Creatine Transporter DefectCREAT_criteriaNCT06018519
Relevant Outcome Measures for Creatine Transporter Deficiency Patient
A study testing Clinical endpoints, Parental questionnaires and Quality of life scale in people with Creatine Transporter Defect, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Creatine transport deficiency (CTD) is a rare genetic disorder related to pathogenic variants in the SLC6A8 gene, located on chromosome Xq28. Clinical diagnosis of CTD is based on clinical presentation, an increased urinary creatine/creatinine ratio and a severe decreased creatine peak on 1H-MRS magnetic resonance… Read more about this study
- Who is it for?
- Ages 2 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Creatine Transporter Defect
- What is being tested?
- Clinical endpoints, Parental questionnaires and Quality of life scale
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 197 participants
- Where
- 1 siteFrance
- Study dates
- 13 Mar 2023to 13 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 60 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Male CTD patients (n=24)
- Male CTD patients having a confirmed mutation in the SLC6A8 gene,
- Aged > 5 to < 35 years
- Whose maternal language is French,
- Having signed the informed consent and/or for whom parents/legal guardian have signed the informed consent,
- Affiliated to national Health Insurance system or parents/legal guardian affiliated to national health insurance system.
Show all 55Show fewer
- Female CTD patients (n=15)
- Female CTD patients having a confirmed mutation in the SLC6A8 gene,
- Aged > 5 to < 60 years,
- Whose maternal language is French,
- Having signed the informed consent and/or for whom parents/legal guardian have signed the informed consent.
- Affiliated to national Health Insurance system (sécurité sociale) or parents/legal guardian affiliated to national health insurance system
- Sex- and chronological age-matched controls (n=24)
- Male
- Aged > 5 to < 35 years
- Whose maternal language is French,
- Having signed the informed consent and/or for whom parents/legal guardian have signed the informed consent,
- Affiliated to national health insurance system or parents/legal guardian affiliated to national health insurance system.
- Sex- and chronological age-matched female controls (n=15)
- female,
- Aged > 5 to < 60 years,
- Whose maternal language is French,
- Having signed the informed consent and/or for whom parents/legal guardian have signed the informed consent
- Affiliated to national Health Insurance system (sécurité sociale) or parents/legal guardian affiliated to national health insurance system
- Sex- and mental age-matched controls (n=39)
- Male and female
- Aged > 2 to < 8 years
- Whose maternal language is French,
- For whom parents/legal guardian have signed the informed consent,
- Affiliated to national health insurance system or parents/legal guardian affiliated to national health insurance system.
- Typically developed children (n=80)
- Male and female
- Aged > 2 to < 8 years
- Whose maternal language is French,
- For whom parents/legal guardian have signed the informed consent,
- Affiliated to national health insurance system or parents/legal guardian affiliated to national health insurance system.
- Sex- and chronological age-matched controls and Sex- and mental age-matched controls, aged < 8 years, could also be included in the Typically developed children group, as the data from the Typically developed children are only necessary to complete the developmental trajectory of the new tasks.
- Non-inclusion Criteria:
- CTD patients (n=39):
- Having a contraindication to the MRI examination (people using a pacemaker or an insulin pump, people wearing a metal prosthesis or an intracerebral clip, and claustrophobic subjects),
- Refusal of the subject and/or the subject's parents to be informed of possible abnormalities detected by MRI,
- Refusal of the subject and/or the subject's parents/legal guardian to be informed of possible abnormalities detected during the cardiac assessment.
- Sex- and chronological age-matched controls (n=39)
- History of neurological or psychiatric disorder,
- Repetition of a grade,
- Learning disability requiring rehabilitation (speech therapy, psychomotor or oculomotor therapy),
- For participants agreeing on performing the MRI examination, having a contraindication to the MRI examination (use of a pacemaker or an insulin pump, people wearing a metal prosthesis or an intracerebral clip, and claustrophobic subjects) and refusal of the subject and/or the subject's parents/legal guardian to be informed of possible abnormalities detected by MRI.
- Sex- and mental age-matched controls (n=39)
- History of neurological or psychiatric disorder,
- Repetition of a grade,
- Learning disability requiring rehabilitation (speech therapy, psychomotor or oculomotor therapy).
- Typically developed children (n=80)
- History of neurological or psychiatric disorder,
- Repetition of a grade,
- Learning disability requiring rehabilitation (speech therapy, psychomotor or oculomotor therapy).
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Woman, mother and child hospital, Hospices Civils de Lyon
Bron, 69500
Aurore CURIE, MD,PhD, 06 70 62 69 76 ext. +33, aurore.curie@chu-lyon.fr
Aurore CURIE, MD,PhD
About this study
Official title: A Prospective Study in Creatine Transporter Deficiency (SLC6A8) Patients to Determine the Most Relevant Outcome Measures
Creatine transport deficiency (CTD) is a rare genetic disorder related to pathogenic variants in the SLC6A8 gene, located on chromosome Xq28. Clinical diagnosis of CTD is based on clinical presentation, an increased urinary creatine/creatinine ratio and a severe decreased creatine peak on 1H-MRS magnetic resonance spectroscopy.
A retrospective study with questionnaires identified that most CTD patients had moderate to severe intellectual disability. Less than one third of patients were able to speak in sentences. Seizures were present in 59% of the patients. 41% had autistic features. Motor dysfunction was mentioned in 58%, and gastrointestinal symptoms were reported in 35% of the patients.
Read more
Several new therapeutic avenues are currently emerging in this disease for which no treatment has been available until now : cyclocreatine (interesting but unfortunately with very little clinical applicability due to its toxicity; dodecyl creatine ester incorporated into lipid nanocapsules with intranasal administration; pharmaco-chaperoning (for the folding-deficient creatine transporter variants, Ultragenyx pharmaceuticals new prodrug designed to deliver creatine to the brain (UX068). These new pharmacological treatment options may offer future opportunities to improve cognition in CTD patients.
A key issue is to determine outcome measures that are accessible to these patients, despite the importance of their cognitive deficit. In a preliminary study (on 31 CTD patients), investigators showed for example, that 75% of patients were unable to perform a Wechsler scale, which is one of the most used neuropsychological test to determine patient IQ (intelligence quotient). Most of the existing cognitive tests were developed to distinguish typically developing persons and ID (intellectual disability) patients, leading to a floor effect in the latter who systematically fail these tests. Therefore, these tests are not adapted to capture the potential effect of a drug in ID patient group. The identification of reliable and sensitive outcome measures for use in clinical trials in ID patients was recognized as a priority in a meeting convened by the NIH. N-of-1 trials (also called Single-Case Experimental Designs or SCEDs) appear of great interest for rare diseases, statistical power coming from the number of repeated measures, which leads to choose outcome measures that can be repeated multiple times.
This innovative study will allow to efficiently preparing future therapeutic trials, by specifying the phenotype of the patients, and by determining the most adapted outcome measures taking into account their cognitive deficiency and the type of experimental design to be used in the context of rare diseases.
- Conditions
- Creatine Transporter Defect
- Being tested
- Clinical endpoints, Parental questionnaires, Quality of life scale, Cognitive assessments, Language assessments
- Keywords
- Creatine Transporter Deficiency (SLC6A8), Outcome measures, Therapeutics, Feasibility, Relevance
- Medical subject headings
- Creatine deficiency, X-linked
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinical endpointsOther
- Number of epileptic seizures
- Change in antiepileptic treatment (increase or decrease)
- Visual analogical scale on a target symptom defined with the parents,
- CGI,
- Actimetry data over 24 hours,
- Podometry data over 24 hours,
- 6 minutes' walk test,
- Clinical examination
- Feasibility of performing an MRI without any anesthesia on a mock scanner
Parental questionnairesOther
10- Adaptive assessment with Vineland Adaptive Behavior scale II,
11- Mac Arthur questionnaire regarding language,
12- Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS),
13- Dunn sensory profile,
14- Aberrant Behavior Checklist,
15- Nisonger Child Behavior Rating form,
16- Social Responsiveness Scale 2,
17- Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)
Quality of life scaleOther
18- Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)
Cognitive assessmentsOther
19- Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible
20- CPM-BF
21- Simple reasoning task on tablet (match-to-sample task)
22- Implicit rules learning (modified Brixton),
23- 4 sub-tests from the WPPSI-IV ("zoo location" to assess spatial memory, "block design" to assess visuo-constructive abilities, "bug search" , "cancellation"),
24- Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention),
25- Elementary visuo-spatial perception (on tablets)
Language assessmentsOther
26- EXALANG 3-6 (10 sub-tests testing for expressive and receptive language assessments),
27- PPVT-5 (receptive vocabulary), EVT-3 (expressive vocabulary),
28- Automatic language analysis (during a 10 minutes interaction, play).
Motor assessmentsOther
29- Kinematic task (specifically designed),
30- Purdue-Pegboard test,
31- Renzi test
Social assessmentsOther
32- Eye-tracking analysis of social visual scenes and social preference index (movies),
33- theory of mind assessment,
34- ADOS scale (Autism Spectrum Disorder),
35- sensitivity to inequality,
36- pro-social behaviors (help of the psychologist)
3T MRIOther
37- Structural, metabolic and functional data
Cardiac assessmentsOther
38- ECG
39- Ultrasound
Biological collectionOther
40- Blood sample
41- Urinary sample
42- Superficial skin biopsy
| Study group | Role | What they receive |
|---|---|---|
| CTD male patients | Other | Case group 24 male CTD patients having a confirmed mutation in the SLC6A8 gene, aged > 5 to < 35 years. Receives: Other: Clinical endpoints; Other: Parental questionnaires; Other: Quality of life scale; Other: Cognitive assessments; Other: Language assessments; Other: Motor assessments; Other: Social assessments; Other: 3T MRI; Other: Cardiac assessments; Other: Biological collection |
| Sex and chronological age matched male controls | Other | Control group 24 male, sex and chronological age matched controls, aged > 5 to < 35 years Receives: Other: Clinical endpoints; Other: Cognitive assessments; Other: Language assessments; Other: Motor assessments; Other: Social assessments; Other: 3T MRI; Other: Biological collection |
| Sex and mental age matched male controls | Other | Control group 24 male, sex and mental age matched controls, aged > 2 to < 8 years Receives: Other: Clinical endpoints; Other: Cognitive assessments; Other: Language assessments; Other: Motor assessments; Other: Social assessments |
| Typically developed children | Other | Control group 80 typically developed children aged > 2 to < 8 years, which corresponds to the mental age of CTD patients.
40 children aged > 2 to < 5 years, and 40 children aged > 6 to < 8 years will perform the newly developed outcome measures. Receives: Other: Cognitive assessments; Other: Language assessments; Other: Motor assessments; Other: Social assessments |
| CTD female patients | Other | 15 female CTD patients having a confirmed mutation in the SLC6A8 gene, aged >5 to < 60 years Receives: Other: Clinical endpoints; Other: Parental questionnaires; Other: Quality of life scale; Other: Cognitive assessments; Other: Language assessments; Other: Motor assessments; Other: Social assessments; Other: 3T MRI; Other: Cardiac assessments; Other: Biological collection |
| Sex and mental age matched female controls | Other | Control group 15 female, sex and mental age matched controls, aged > 2 to < 8 years Receives: Other: Clinical endpoints; Other: Cognitive assessments; Other: Language assessments; Other: Motor assessments; Other: Social assessments |
| Sex and chronological age matched female controls | Other | Control group 15 female, sex and chronological age matched controls, aged > 5 to < 60 years Receives: Other: Clinical endpoints; Other: Cognitive assessments; Other: Language assessments; Other: Motor assessments; Other: Social assessments; Other: 3T MRI; Other: Biological collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical endpoints : number of epileptic seizures
Number of epileptic seizures
Measured: Up to 90 Days
Clinical endpoints : antiepileptic treatment
Change in antiepileptic treatment (increase or decrease)
Measured: For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).
Clinical endpoints : Visual analogical scale
Visual analogical scale on a target symptom defined with the parents,
Measured: Up to 90 Days
Clinical endpoints : actimetry
Actimetry data over 48 hours
Measured: Up to 90 Days
Clinical endpoints : podometry
Podometry data over 24 hours
Measured: Up to 90 Days
Clinical endpoints : walk test
6 minutes' walk test
Measured: Up to 90 Days
Clinical endpoints : Clinical examination
Clinical examination
Measured: For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).
Clinical endpoints :Feasibility of performing an MRI
Feasibility of performing an MRI without any anesthesia on a mock scanner
Measured: For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).
Parental questionnaires : Vineland Adaptive Behavior scale II
Adaptive assessment with Vineland Adaptive Behavior scale II
Measured: For all 24 CTD patients: V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).
Parental questionnaires : Mac Arthur questionnaire
Mac Arthur questionnaire regarding language
Measured: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).
Parental questionnaires : PDD-MRS
Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS)
Measured: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).
Parental questionnaires : Dunn sensory profile
Dunn sensory profile
Measured: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).
Parental questionnaires : Aberrant Behavior Checklist
Aberrant Behavior Checklist
Measured: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).
Parental questionnaires : Nisonger Child Behavior Rating form
Nisonger Child Behavior Rating form
Measured: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).
Parental questionnaires : Social Responsiveness Scale 2
Social Responsiveness Scale 2
Measured: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).
Parental questionnaires : impact on primary caregiver
Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)
Measured: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).
Quality of life scale
Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)
Measured: For all 24 CTD patients: At V1 (Day1/Day2) For 9 out of 24 CTD patients: Repeated at V3 (Day30) and V7 (Day90).
Cognitive assessments : Leiter 3 scale
Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible
Measured: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
Cognitive assessments : CPM-BF
CPM-BF : Raven's coloured Progressive Matrices
Measured: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
Cognitive assessments : reasoning task
Simple reasoning task on tablet (match-to-sample task)
Measured: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
Cognitive assessments : Implicit rules learning
Implicit rules learning (modified Brixton),
Measured: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
Cognitive assessments : WPPSI-IV
4 sub-tests from the WPPSI-IV ("zoo location" to assess spatial memory, "block design" to assess visuo-constructive abilities, "bug search" , "cancellation"),
Measured: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
Cognitive assessments : Attention assessment
Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention),
Measured: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
Cognitive assessments : Elementary visuo-spatial perception
Elementary visuo-spatial perception (on tablets)
Measured: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
Language assessments : EXALANG 3-6
EXALANG 3-6 - Computerized battery for the evaluation of oral and written language : 10 sub-tests testing for expressive and receptive language assessments
Measured: For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)
Language assessments : vocabulary
PPVT-5 : Peabody Picture Vocabulary Test Fifth Edition = receptive vocabulary, EVT-3 : Expressive Vocabulary Test third edition,
Measured: For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)
Language assessments : Automatic language analysis
Automatic language analysis (during a 10 minutes interaction, play).
Measured: For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)
Motor assessments : Kinematic task
Kinematic task (specifically designed)
Measured: CTD patients : performed at V1 (Day1/Day2). Controls: Motor assessment at V1 (Day 1)
Motor assessments : Purdue-Pegboard test
Purdue-Pegboard test
Measured: CTD patients : performed at V1 (Day1/Day2), V3(Day30), and V7 (Day90). Controls: Motor assessment at V1 (Day 1)
Motor assessments : Renzi test
Renzi test
Measured: CTD patients : performed at V1 (Day1/Day2), V3(Day30), and V7 (Day90). Controls: Motor assessment at V1 (Day 1)
Social assessments : Eye-tracking
Eye-tracking analysis of social visual scenes and social preference index (movies)
Measured: CTD patients : performed at V1 (Day1/Day2), V3 (Day30) and V7 (Day90). Controls : Social assessment at V1(Day1)
Social assessments : Theory of mind assessment
Theory of mind assessment
Measured: CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)
Social assessments : ADOS scale (Autism Diagnostic Observation Scale)
ADOS scale (Autism Spectrum Disorder)
Measured: CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)
Social assessments : Sensitivity to inequality
Sensitivity to inequality
Measured: CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)
Social assessments : Pro-social behaviors (help of the psychologist)
Pro-social behaviors (help of the psychologist)
Measured: CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)
Secondary outcomes (7)
Neuroimaging (MRI)
The MRI will be performed to describe structural and functional neuroanatomical profile of CTD patient in comparison to chronological age-matched controls and variability in creatine peak assessment using MR spectroscopy
Measured: V1 (Day1/Day2)
Cardiac assessments : Electrocardiogram
Electrocardiogram (ECG) will be performed to describe CTD patients cardiac profile (especially the risk of increased QTC and/or cardiac echography abnormality)
Measured: CTD patients: V1 (Day1/Day2)
Cardiac assessments : Ultrasound
Cardiac Ultrasound will be performed to describe CTD patients cardiac profile (especially the risk of increased QTC and/or cardiac echography abnormality)
Measured: CTD patients: V1 (Day1/Day2)
Biological collection : Blood sample
Blood sample (plasma and peripheral blood mononuclear cells)
Measured: CTD patients: V1 (Day1/Day2)
Biological collection : Urine sample
Urine sample will be collected to create a collection of biological samples associated with clinical and genomic data from CTD patients. In the future this will be usefull for research labs to investigate new biomarkers (not identified yet) or to test for the efficiency of new therapeutic approaches in vitro (on cultivated fibroblasts or after the development of iPS cells or organoïds) in this rare disease.
Measured: CTD patients: V1 (Day1/Day2)
Biological collection : Superficial skin biopsy
Superficial skin biopsy will be performed to get cultivated fibroblasts to create a collection of biological samples associated with clinical and genomic data from CTD patients. In the future this will be usefull for research labs to investigate new biomarkers (not identified yet) or to test for the efficiency of new therapeutic approaches in vitro (on cultivated fibroblasts or after the development of iPS cells or organoïds) in this rare disease.
Measured: CTD patients: V1 (Day1/Day2)
Biological collection : biological profile of DTC patients compared to sex- and chronological age-matched controls
To describe the biological profile of DTC patients compared to sex- and chronological age-matched controls.
Biological profile will be performed for CTD patients and the sex- and chronological age- matched controls who agreed on participating to the biological collection.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2023
- Study start13 Mar 2023
- Primary completion13 Dec 2028 (estimated)
- Study completion13 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Creatine Transporter DefectStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 197 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06018519
- Sponsor's protocol ID
- 69HCL21_0655
- Other IDs
- 2022-A02063-40
- Acronym
- CREAT_criteria
- Status last verified
- Nov 2025
- First submitted
- 3 Nov 2022
- Last updated
- 27 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Study in Creatine Transporter Deficiency (SLC6A8) Patients to Determine the Most Relevant Outcome Measures
- ClinicalTrials.gov ID
- NCT06018519
- Acronym / sponsor ID
- CREAT_criteria / 69HCL21_0655
- Conditions
- Creatine Transporter Defect
- Keywords
- Creatine Transporter Deficiency (SLC6A8), Outcome measures, Therapeutics, Feasibility, Relevance
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 197 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 13 Mar 2023 (actual)
- Primary completion
- 13 Dec 2028 (estimated)
- Study completion
- 13 Dec 2028 (estimated)
- First posted
- 30 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Creatine transport deficiency (CTD) is a rare genetic disorder related to pathogenic variants in the SLC6A8 gene, located on chromosome Xq28. Clinical diagnosis of CTD is based on clinical presentation, an increased urinary creatine/creatinine ratio and a severe decreased creatine peak on 1H-MRS magnetic resonance spectroscopy.
A retrospective study with questionnaires identified that most CTD patients had moderate to severe intellectual disability. Less than one third of patients were able to speak in sentences. Seizures were present in 59% of the patients. 41% had autistic features. Motor dysfunction was mentioned in 58%, and gastrointestinal symptoms were reported in 35% of the patients.
Several new therapeutic avenues are currently emerging in this disease for which no treatment has been available until now : cyclocreatine (interesting but unfortunately with very little clinical applicability due to its toxicity; dodecyl creatine ester incorporated into lipid nanocapsules with intranasal administration; pharmaco-chaperoning (for the folding-deficient creatine transporter variants, Ultragenyx pharmaceuticals new prodrug designed to deliver creatine to the brain (UX068). These new pharmacological treatment options may offer future opportunities to improve cognition in CTD patients.
A key issue is to determine outcome measures that are accessible to these patients, despite the importance of their cognitive deficit. In a preliminary study (on 31 CTD patients), investigators showed for example, that 75% of patients were unable to perform a Wechsler scale, which is one of the most used neuropsychological test to determine patient IQ (intelligence quotient). Most of the existing cognitive tests were developed to distinguish typically developing persons and ID (intellectual disability) patients, leading to a floor effect in the latter who systematically fail these tests. Therefore, these tests are not adapted to capture the potential effect of a drug in ID patient group. The identification of reliable and sensitive outcome measures for use in clinical trials in ID patients was recognized as a priority in a meeting convened by the NIH. N-of-1 trials (also called Single-Case Experimental Designs or SCEDs) appear of great interest for rare diseases, statistical power coming from the number of repeated measures, which leads to choose outcome measures that can be repeated multiple times.
This innovative study will allow to efficiently preparing future therapeutic trials, by specifying the phenotype of the patients, and by determining the most adapted outcome measures taking into account their cognitive deficiency and the type of experimental design to be used in the context of rare diseases.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| CTD male patients | Other | Other: Clinical endpoints, Other: Parental questionnaires, Other: Quality of life scale, Other: Cognitive assessments, Other: Language assessments, Other: Motor assessments, Other: Social assessments, Other: 3T MRI, Other: Cardiac assessments, Other: Biological collectionCase group 24 male CTD patients having a confirmed mutation in the SLC6A8 gene, aged > 5 to < 35 years. |
| Sex and chronological age matched male controls | Other | Other: Clinical endpoints, Other: Cognitive assessments, Other: Language assessments, Other: Motor assessments, Other: Social assessments, Other: 3T MRI, Other: Biological collectionControl group 24 male, sex and chronological age matched controls, aged > 5 to < 35 years |
| Sex and mental age matched male controls | Other | Other: Clinical endpoints, Other: Cognitive assessments, Other: Language assessments, Other: Motor assessments, Other: Social assessmentsControl group 24 male, sex and mental age matched controls, aged > 2 to < 8 years |
| Typically developed children | Other | Other: Cognitive assessments, Other: Language assessments, Other: Motor assessments, Other: Social assessmentsControl group 80 typically developed children aged > 2 to < 8 years, which corresponds to the mental age of CTD patients. 40 children aged > 2 to < 5 years, and 40 children aged > 6 to < 8 years will perform the newly developed outcome measures. |
| CTD female patients | Other | Other: Clinical endpoints, Other: Parental questionnaires, Other: Quality of life scale, Other: Cognitive assessments, Other: Language assessments, Other: Motor assessments, Other: Social assessments, Other: 3T MRI, Other: Cardiac assessments, Other: Biological collection15 female CTD patients having a confirmed mutation in the SLC6A8 gene, aged >5 to < 60 years |
| Sex and mental age matched female controls | Other | Other: Clinical endpoints, Other: Cognitive assessments, Other: Language assessments, Other: Motor assessments, Other: Social assessmentsControl group 15 female, sex and mental age matched controls, aged > 2 to < 8 years |
| Sex and chronological age matched female controls | Other | Other: Clinical endpoints, Other: Cognitive assessments, Other: Language assessments, Other: Motor assessments, Other: Social assessments, Other: 3T MRI, Other: Biological collectionControl group 15 female, sex and chronological age matched controls, aged > 5 to < 60 years |
Who may qualify
- Ages
- 2 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (55 listed)
- Male CTD patients (n=24)
- Male CTD patients having a confirmed mutation in the SLC6A8 gene,
- Aged > 5 to < 35 years
- Whose maternal language is French,
- Having signed the informed consent and/or for whom parents/legal guardian have signed the informed consent,
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clinical endpoints1. Number of epileptic seizures 2. Change in antiepileptic treatment (increase or decrease) 3. Visual analogical scale on a target symptom defined with the parents, 4. CGI, 5. Actimetry data over 24 hours, 6. Podometry data over 24 hours, 7. 6 minutes' walk test, 8. Clinical examination 9. Feasibility of performing an MRI without any anesthesia on a mock scanner | Other | CTD female patients, CTD male patients, Sex and chronological age matched female controls, Sex and chronological age matched male controls, Sex and mental age matched female controls, Sex and mental age matched male controls |
| Parental questionnaires10- Adaptive assessment with Vineland Adaptive Behavior scale II, 11- Mac Arthur questionnaire regarding language, 12- Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS), 13- Dunn sensory profile, 14- Aberrant Behavior Checklist, 15- Nisonger Child Behavior Rating form, 16- Social Responsiveness Scale 2, 17- Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL) | Other | CTD female patients, CTD male patients |
| Quality of life scale18- Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18) | Other | CTD female patients, CTD male patients |
| Cognitive assessments19- Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible 20- CPM-BF 21- Simple reasoning task on tablet (match-to-sample task) 22- Implicit rules learning (modified Brixton), 23- 4 sub-tests from the WPPSI-IV ("zoo location" to assess spatial memory, "block design" to assess visuo-constructive abilities, "bug search" , "cancellation"), 24- Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention), 25- Elementary visuo-spatial perception (on tablets) | Other | CTD female patients, CTD male patients, Sex and chronological age matched female controls, Sex and chronological age matched male controls, Sex and mental age matched female controls, Sex and mental age matched male controls, Typically developed children |
| Language assessments26- EXALANG 3-6 (10 sub-tests testing for expressive and receptive language assessments), 27- PPVT-5 (receptive vocabulary), EVT-3 (expressive vocabulary), 28- Automatic language analysis (during a 10 minutes interaction, play). | Other | CTD female patients, CTD male patients, Sex and chronological age matched female controls, Sex and chronological age matched male controls, Sex and mental age matched female controls, Sex and mental age matched male controls, Typically developed children |
| Motor assessments29- Kinematic task (specifically designed), 30- Purdue-Pegboard test, 31- Renzi test | Other | CTD female patients, CTD male patients, Sex and chronological age matched female controls, Sex and chronological age matched male controls, Sex and mental age matched female controls, Sex and mental age matched male controls, Typically developed children |
| Social assessments32- Eye-tracking analysis of social visual scenes and social preference index (movies), 33- theory of mind assessment, 34- ADOS scale (Autism Spectrum Disorder), 35- sensitivity to inequality, 36- pro-social behaviors (help of the psychologist) | Other | CTD female patients, CTD male patients, Sex and chronological age matched female controls, Sex and chronological age matched male controls, Sex and mental age matched female controls, Sex and mental age matched male controls, Typically developed children |
| 3T MRI37- Structural, metabolic and functional data | Other | CTD female patients, CTD male patients, Sex and chronological age matched female controls, Sex and chronological age matched male controls |
| Cardiac assessments38- ECG 39- Ultrasound | Other | CTD female patients, CTD male patients |
| Biological collection40- Blood sample 41- Urinary sample 42- Superficial skin biopsy | Other | CTD female patients, CTD male patients, Sex and chronological age matched female controls, Sex and chronological age matched male controls |
Primary outcome
Clinical endpoints : number of epileptic seizures
Time frame: Up to 90 Days
Number of epileptic seizures
Clinical endpoints : antiepileptic treatment
Time frame: For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).
Change in antiepileptic treatment (increase or decrease)
Clinical endpoints : Visual analogical scale
Time frame: Up to 90 Days
Visual analogical scale on a target symptom defined with the parents,
Clinical endpoints : actimetry
Time frame: Up to 90 Days
Actimetry data over 48 hours
Clinical endpoints : podometry
Time frame: Up to 90 Days
Podometry data over 24 hours
Clinical endpoints : walk test
Time frame: Up to 90 Days
6 minutes' walk test
Clinical endpoints : Clinical examination
Time frame: For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).
Clinical examination
Clinical endpoints :Feasibility of performing an MRI
Time frame: For all 24 CTD patients: all examinations at V1 (Day 1/Day2) For 9 out of 24 CTD patients: examinations repeated every two weeks at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).
Feasibility of performing an MRI without any anesthesia on a mock scanner
Parental questionnaires : Vineland Adaptive Behavior scale II
Time frame: For all 24 CTD patients: V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).
Adaptive assessment with Vineland Adaptive Behavior scale II
Parental questionnaires : Mac Arthur questionnaire
Time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).
Mac Arthur questionnaire regarding language
Parental questionnaires : PDD-MRS
Time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).
Pervasive Development Disorder in Mentally Retarded persons Scale (PDD-MRS)
Parental questionnaires : Dunn sensory profile
Time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).
Dunn sensory profile
Parental questionnaires : Aberrant Behavior Checklist
Time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90).
Aberrant Behavior Checklist
Parental questionnaires : Nisonger Child Behavior Rating form
Time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).
Nisonger Child Behavior Rating form
Parental questionnaires : Social Responsiveness Scale 2
Time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V7 (Day90).
Social Responsiveness Scale 2
Parental questionnaires : impact on primary caregiver
Time frame: For all 24 CTD patients: at V1 (Day1/Day2), For 9 out 24 CTD patients: repeated at V3 (Day30) and V7 (Day90).
Scales assessing the impact on primary caregiver (CBI-M/ Beach Center Family QOL)
Quality of life scale
Time frame: For all 24 CTD patients: At V1 (Day1/Day2) For 9 out of 24 CTD patients: Repeated at V3 (Day30) and V7 (Day90).
Quality of life scale (PedsQL 4.0 for children or San Martin scale if the patient is older than 18)
Cognitive assessments : Leiter 3 scale
Time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
Leiter 3 scale (4 cognitive sub-tests to be able to compute the non-verbal IQ and 2 non-verbal memory sub-tests) or Bayley 4 if Leiter 3 is not possible
Cognitive assessments : CPM-BF
Time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
CPM-BF : Raven's coloured Progressive Matrices
Cognitive assessments : reasoning task
Time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
Simple reasoning task on tablet (match-to-sample task)
Cognitive assessments : Implicit rules learning
Time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
Implicit rules learning (modified Brixton),
Cognitive assessments : WPPSI-IV
Time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
4 sub-tests from the WPPSI-IV ("zoo location" to assess spatial memory, "block design" to assess visuo-constructive abilities, "bug search" , "cancellation"),
Cognitive assessments : Attention assessment
Time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V3 (Day30) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
Attention assessment (4 sub-tests from KITTAP: alert, go/no go, flexibility, divided attention),
Cognitive assessments : Elementary visuo-spatial perception
Time frame: For the 24 CTD patients: at V1 (Day1/Day2), For 9 out of 24 CTD patients: repeated at V2 (Day15), V3 (Day30), V4 (Day45), V5 (Day60), V6 (Day75) and V7 (Day90). Controls: Cognitive assessment at V1(Day 1)
Elementary visuo-spatial perception (on tablets)
Language assessments : EXALANG 3-6
Time frame: For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)
EXALANG 3-6 - Computerized battery for the evaluation of oral and written language : 10 sub-tests testing for expressive and receptive language assessments
Language assessments : vocabulary
Time frame: For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)
PPVT-5 : Peabody Picture Vocabulary Test Fifth Edition = receptive vocabulary, EVT-3 : Expressive Vocabulary Test third edition,
Language assessments : Automatic language analysis
Time frame: For all 24 CTD patients: performed at V1 (Day1/Day2). For 9 out of 24 CTD patients: repeated at V3 (Day30), and V7 (Day90). Controls: Language assessment at V1(Day 1)
Automatic language analysis (during a 10 minutes interaction, play).
Motor assessments : Kinematic task
Time frame: CTD patients : performed at V1 (Day1/Day2). Controls: Motor assessment at V1 (Day 1)
Kinematic task (specifically designed)
Motor assessments : Purdue-Pegboard test
Time frame: CTD patients : performed at V1 (Day1/Day2), V3(Day30), and V7 (Day90). Controls: Motor assessment at V1 (Day 1)
Purdue-Pegboard test
Motor assessments : Renzi test
Time frame: CTD patients : performed at V1 (Day1/Day2), V3(Day30), and V7 (Day90). Controls: Motor assessment at V1 (Day 1)
Renzi test
Social assessments : Eye-tracking
Time frame: CTD patients : performed at V1 (Day1/Day2), V3 (Day30) and V7 (Day90). Controls : Social assessment at V1(Day1)
Eye-tracking analysis of social visual scenes and social preference index (movies)
Social assessments : Theory of mind assessment
Time frame: CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)
Theory of mind assessment
Social assessments : ADOS scale (Autism Diagnostic Observation Scale)
Time frame: CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)
ADOS scale (Autism Spectrum Disorder)
Social assessments : Sensitivity to inequality
Time frame: CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)
Sensitivity to inequality
Social assessments : Pro-social behaviors (help of the psychologist)
Time frame: CTD patients : performed at V1 (Day1/Day2). Controls : Social assessment at V1(Day1)
Pro-social behaviors (help of the psychologist)
7 secondary outcomes
Neuroimaging (MRI)
Time frame: V1 (Day1/Day2)
Cardiac assessments : Electrocardiogram
Time frame: CTD patients: V1 (Day1/Day2)
Cardiac assessments : Ultrasound
Time frame: CTD patients: V1 (Day1/Day2)
Biological collection : Blood sample
Time frame: CTD patients: V1 (Day1/Day2)
Biological collection : Urine sample
Time frame: CTD patients: V1 (Day1/Day2)
Biological collection : Superficial skin biopsy
Time frame: CTD patients: V1 (Day1/Day2)
Biological collection : biological profile of DTC patients compared to sex- and chronological age-matched controls
Time frame: Up to 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Clinical endpoints, Parental questionnaires and Quality of life scale in people with Creatine Transporter Defect, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 55 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aurore CURIE, MD,PhD (06 70 62 69 76 ext. +33, aurore.curie@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical endpoints : number of epileptic seizures (time frame: Up to 90 Days). The study lists 35 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.