ADNP SyndromePhase 1/2NCT04388774
Low-Dose Ketamine in Children With ADNP Syndrome
A Phase 1/2 study testing Ketamine in people with ADNP Syndrome, run by Alexander Kolevzon at 1 site in United States.
Trial summary
This is a Phase 2A, single dose, open-label study to evaluate the safety, tolerability, and efficacy of a low-dose, 40-minute infusion into the veins (intravenous infusion or "IV") of ketamine in children with ADNP syndrome (Activity-Dependent Neuroprotective Protein). Read more about this study
- Who is it for?
- Ages 5 to 12 years
- Conditions the study is for
- ADNP Syndrome
- What is being tested?
- Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Aug 2020to 8 Jun 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 5 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 5 to 12 years old (inclusive) at the time of informed consent;
- Has a diagnosis of ADNP syndrome, confirmed by genetic testing prior to subject randomization;
- Has a Clinical Global Impression-Severity score of 4 (moderately ill) or greater at screening;
- Any concomitant medication, including anti-epileptic and/or behavioral medications, supplements, and special diets, must be at a stable dose for at least 4 weeks before;
- Has an English-speaking caregiver capable of providing informed consent and able to attend all scheduled study visits, oversee the administration of study drug, and provide feedback regarding the subject's behavior and other symptoms as described in the protocol;
- Provide assent to the protocol (when applicable);
- Has a caregiver who will agree not to post any of the subject's personal medical data related to the study or information related to the study on any website or social media site (e.g., Facebook and Twitter) until they have been notified that the study is completed.
- Age-specific blood pressure parameters for inclusion in the study will be based on established guidelines.
Who cannot join
- Has a concomitant disease (e.g., gastrointestinal, renal, hepatic, endocrine, respiratory, or cardiovascular system disease) or condition or any clinically significant finding at screening that could interfere with the conduct of the study or that would pose an unacceptable risk to the subject in this study;
- Has clinically significant lab abnormalities or vital signs at the time of screening (e.g., alanine aminotransferase or aspartate aminotransferase >2.5 × upper limit of normal; total bilirubin or creatinine >1.5 × upper limit of normal). Re-testing of safety labs is allowed;
- Hypertension that is not well controlled (systolic BP >130-140 mm Hg or diastolic BP >85-95 mm Hg depending on age);
- A blood pressure reading over 160/90 or two separate readings over 140/90 at screening or baseline visits;
- Thyroid impairment, as reflected by a TSH > 4.2 mU/L;
- Cardiac disease, as reflected by an EKG that is abnormal and of concern for cardiac disease;
Show all 11Show fewer
- Has had changes in his/her medication regimen within the previous month;
- Has a history of uncontrollable seizure disorder or seizure episodes within 1 month of screening;
- Has a history of suicidal behavior or considered by the investigator to be at high risk of suicide;
- Has a current or past history of psychotic symptoms;
- Has enrolled in any clinical trial or used of any investigational agent, device, and/or investigational procedure within the 30 days before screening or does so concurrently with this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: A Phase 2A Open-Label Study Evaluating the Safety and Efficacy of Low-Dose Ketamine in Children With ADNP Syndrome
This is a Phase 2A, single dose, open-label study to evaluate the safety, tolerability, and efficacy of a low-dose, 40-minute infusion into the veins (intravenous infusion or "IV") of ketamine in children with ADNP syndrome (Activity-Dependent Neuroprotective Protein). The study team will enroll 10 participants, ages 5 to 12, at Mount Sinai. The study participation is expected to last 4 weeks and will include 5 scheduled clinic visits in order to complete safety monitoring, clinical assessments, and biomarker collection. At the conclusion of this study, the study team expects to demonstrate the safety and tolerability of low-dose ketamine in children with ADNP syndrome. Additionally, the study team anticipates identifying meaningful signals of efficacy in clinical outcome measures using RNA and DNA sequencing to analyze ADNP protein expression and DNA methylation profiles, a natural process by which methyl groups are added to the DNA to change its activity, in order to assess sensitivity to change with low-dose ketamine treatment and inform future phase 3 studies. Ketamine is not currently approved by the Food and Drug Administration to treat this syndrome, but it is approved for use in children in other situations, for example in anesthesia.
- Conditions
- ADNP Syndrome
- Being tested
- Ketamine
- Keywords
- Ketamine, ADNP, Activity-Dependent Neuroprotector Protein, Chromosome Disorders, Chromosome Aberrations
- Medical subject headings
- Chromosome Disorders, Chromosome Aberrations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
A single 40-minute intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Total dose administration or 0.5 mg/kg of ketamine Receives: Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With an Adverse Event
Number of Participants with an adverse event as defined by the Systematic Longitudinal Assessment of Adverse Events (SLAES) which is a comprehensive form that assesses medical and behavioral conditions that were present at screening and/or baseline. Conditions are considered treatment emergent if their severity increased significantly after the participant had taken at least one dose of the study treatment. Treatment emergent adverse events will be tracked considered in the adverse event safety analysis. Severity of adverse events are categorized as mild, moderate, severe, life-threatening, or resulting in death and the treating physician indicates if the adverse event was related or unrelated to study drug.
Measured: Week 4
Secondary outcomes (12)
Aberrant Behavior Checklist
Changes in scale at week 1 compared to baseline. Aberrant Behavior Checklist is a behavior rating scale for the assessment of treatment effects. Each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). Subscales from 0-45 for Irritability; 0-48 for Social Withdrawal and Hyperactivity; from 0-21 for Stereotypy; and 0-12 for In Speech , with total scale from 0 to 48, with higher score indicating worse health outcomes.
Measured: Baseline, Week 1
Anxiety, Depression and Mood Scales (ADAMS)
The ADAMS is a parent/caregiver-completed measure and consists of 28 items, grouped into five subscales (Manic/Hyperactive Behavior, Depressed Mood, Social Avoidance, General Anxiety, Obsessive Behavior), and scored on a four-point Likert scale that combines frequency and severity ratings from 0-3. Subscales range - Hyperactivity 0-15; Depressed 0-21; Social Avoidance 0-21; General anxiety 0-21; OCD 0-9. Scores are not summed. Higher score indicates poorer health outcomes.
Measured: Baseline and Week 1
Repetitive Behavior Scale-Revised (RBS-R)
Change in repetitive behaviors at weeks 1 compared to baseline. RBS-R subscales - Stereo 0-18; Self injury 0-24; Compulsive 0-24; Ritualistic 0-18; Sameness 0-33; Restricted 0-12. Total scale range from 0 to 126 with higher score indicating worse health outcomes.
Measured: Baseline, Week 1
Clinical Global Impressions - Improvement Scale (CGI-I)
Changes in scale at weeks 2, and 4 compared to baseline. Clinical Global impressions - Improvement Scale is anchored to symptoms of ADNP syndrome for the assessment of treatment effects. CGI-I total score from 1 to 7 point scale, with higher score indicating worse health outcomes.
Measured: Baseline, Week 2, and Week 4
Childrens Sleep Habits Questionnaire
Change in sleep habits at week 1 compared to baseline. Full scale from 0 to 110, with higher score indicating worse health outcomes.
Measured: Baseline, Week 1
Peabody Picture Vocabulary Test and Expressive Vocabulary Test
Expressive and receptive language assessed by Peabody Picture Vocabulary Test and Expressive Vocabulary Test at Day 1, Weeks 1, 2, and 4. Full scale from 40 to 160, with higher score indicating better health outcomes.
Measured: Baseline, Week 1, Week 2, and Week 4
Proportion of Target-First Trials Saccades
Change at Day 1 and Week 1 as compared to baseline using computerized eye tracking to record where the subject is looking during an activity in which the subject will see a video of a person with two objects, turning her head towards one of the objects, the target.
Mean proportion of trials in which participants made saccades to the target before the distractor.
Measured: Baseline, Day 1, Week 1
Latency to First Saccade
Change at week 1, week 2, and week 4 as compared to baseline using computerized eye tracking to record where the subject is looking during an activity in which the subject will see different social and non-social stimuli.
Latency to first saccade to the target
Measured: Baseline, Day 1, Week 1
Proportion of Target-Dwelling
Change at Day 1 and Week 1 as compared to baseline using computerized eye tracking to record where the subject is looking during an activity in which the subject will see different social and non-social stimuli.
Proportion of time participants spent dwelling on the target versus distractor.
Measured: Baseline, Day 1, Week 1
Electrophysiology Recording
Electroencephalographic recordings to measure Auditory Event Related Potentials at baseline, week 1, week 2, and week 4.
In separate blocks, participants heard a 500-ms click at either a stimulation rate of 40 or 20 Hz. Click trains were presented 150 times each, with an intertrial interval of 50 ms, at approximately 60 db.
Higher number indicates higher amplitude neural response to auditory stimuli.
Measured: Baseline, Week 1, Week 2, and Week 4
Vineland Adaptive Behavior Scales
Changes in scale at week 4 compared to baseline. Vineland Adaptive Behavior Scales measures adaptive functioning. Higher score indicating better health outcomes. Domain scores are standard scores - population mean 100 standard deviation 15.
an overall composite score, it consists of three subscales: (a) communication (receptive, expressive, written), (b) socialization (interpersonal relationships, play and leisure, coping skills), and (c) daily living (person, domestic, community).
Measured: Baseline and Week 4
Caregiver Strain Questionnaire (CGSQ)
Caregiver Strain Questionnaire (CGSQ) is a 13 question tool, with a 5-point Likert scale ranging from Not at all (0) to Very much (4). Domains (Objective strain, Subjective externalized strain, Subjective internalized strain) are averaged scores, range from 0-4. Total score (Global score) is a sum of the three subdomains. Full scale range 0-12, higher score indicates more severe strain.
Measured: Baseline and Week 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2020
- Study start19 Aug 2020
- Primary completion8 Jun 2021
- Study completion8 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ADNP SyndromeStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alexander Kolevzon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Alexander Kolevzon, Icahn School of Medicine at Mount Sinai
- Investigators
- Alexander Kolevzon, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04388774
- Sponsor's protocol ID
- GCO 20-1253
- Status last verified
- Jul 2023
- First submitted
- 12 May 2020
- Last updated
- 7 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2A Open-Label Study Evaluating the Safety and Efficacy of Low-Dose Ketamine in Children With ADNP Syndrome
- ClinicalTrials.gov ID
- NCT04388774
- Acronym / sponsor ID
- GCO 20-1253
- Conditions
- ADNP Syndrome
- Keywords
- Ketamine, ADNP, Activity-Dependent Neuroprotector Protein, Chromosome Disorders, Chromosome Aberrations
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Alexander KolevzonUniversity, hospital or other
- Study start
- 19 Aug 2020 (actual)
- Primary completion
- 8 Jun 2021 (actual)
- Study completion
- 8 Jun 2021 (actual)
- First posted
- 14 May 2020 (actual)
- Results
- Posted 7 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2A, single dose, open-label study to evaluate the safety, tolerability, and efficacy of a low-dose, 40-minute infusion into the veins (intravenous infusion or "IV") of ketamine in children with ADNP syndrome (Activity-Dependent Neuroprotective Protein). The study team will enroll 10 participants, ages 5 to 12, at Mount Sinai. The study participation is expected to last 4 weeks and will include 5 scheduled clinic visits in order to complete safety monitoring, clinical assessments, and biomarker collection. At the conclusion of this study, the study team expects to demonstrate the safety and tolerability of low-dose ketamine in children with ADNP syndrome. Additionally, the study team anticipates identifying meaningful signals of efficacy in clinical outcome measures using RNA and DNA sequencing to analyze ADNP protein expression and DNA methylation profiles, a natural process by which methyl groups are added to the DNA to change its activity, in order to assess sensitivity to change with low-dose ketamine treatment and inform future phase 3 studies. Ketamine is not currently approved by the Food and Drug Administration to treat this syndrome, but it is approved for use in children in other situations, for example in anesthesia.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: KetamineTotal dose administration or 0.5 mg/kg of ketamine |
Who may qualify
- Ages
- 5 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 5 to 12 years old (inclusive) at the time of informed consent;
- Has a diagnosis of ADNP syndrome, confirmed by genetic testing prior to subject randomization;
- Has a Clinical Global Impression-Severity score of 4 (moderately ill) or greater at screening;
- Any concomitant medication, including anti-epileptic and/or behavioral medications, supplements, and special diets, must be at a stable dose for at least 4 weeks before;
- Has an English-speaking caregiver capable of providing informed consent and able to attend all scheduled study visits, oversee the administration of study drug, and provide feedback regarding the subject's behavior and other symptoms as described in the protocol;
Key exclusion criteria (11 listed)
- Has a concomitant disease (e.g., gastrointestinal, renal, hepatic, endocrine, respiratory, or cardiovascular system disease) or condition or any clinically significant finding at screening that could interfere with the conduct of the study or that would pose an unacceptable risk to the subject in this study;
- Has clinically significant lab abnormalities or vital signs at the time of screening (e.g., alanine aminotransferase or aspartate aminotransferase >2.5 × upper limit of normal; total bilirubin or creatinine >1.5 × upper limit of normal). Re-testing of safety labs is allowed;
- Hypertension that is not well controlled (systolic BP >130-140 mm Hg or diastolic BP >85-95 mm Hg depending on age);
- A blood pressure reading over 160/90 or two separate readings over 140/90 at screening or baseline visits;
- Thyroid impairment, as reflected by a TSH > 4.2 mU/L;
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 |
|---|---|---|
| KetamineA single 40-minute intravenous infusion | Drug | Ketamine |
Primary outcome
Number of Participants With an Adverse Event
Time frame: Week 4
Number of Participants with an adverse event as defined by the Systematic Longitudinal Assessment of Adverse Events (SLAES) which is a comprehensive form that assesses medical and behavioral conditions that were present at screening and/or baseline. Conditions are considered treatment emergent if their severity increased significantly after the participant had taken at least one dose of the study treatment. Treatment emergent adverse events will be tracked considered in the adverse event safety analysis. Severity of adverse events are categorized as mild, moderate, severe, life-threatening, or resulting in death and the treating physician indicates if the adverse event was related or unrelated to study drug.
12 secondary outcomes
Aberrant Behavior Checklist
Time frame: Baseline, Week 1
Anxiety, Depression and Mood Scales (ADAMS)
Time frame: Baseline and Week 1
Repetitive Behavior Scale-Revised (RBS-R)
Time frame: Baseline, Week 1
Clinical Global Impressions - Improvement Scale (CGI-I)
Time frame: Baseline, Week 2, and Week 4
Childrens Sleep Habits Questionnaire
Time frame: Baseline, Week 1
Peabody Picture Vocabulary Test and Expressive Vocabulary Test
Time frame: Baseline, Week 1, Week 2, and Week 4
Proportion of Target-First Trials Saccades
Time frame: Baseline, Day 1, Week 1
Latency to First Saccade
Time frame: Baseline, Day 1, Week 1
Proportion of Target-Dwelling
Time frame: Baseline, Day 1, Week 1
Electrophysiology Recording
Time frame: Baseline, Week 1, Week 2, and Week 4
Vineland Adaptive Behavior Scales
Time frame: Baseline and Week 4
Caregiver Strain Questionnaire (CGSQ)
Time frame: Baseline and Week 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for ADNP Syndrome
RecruitingObservational study
Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
16P11.2 Deletion Syndrome, 16p11.2 Duplications
RecruitingObservational study
ADNP Syndrome: The Seaver Autism Center for Research and Treatment is Characterizing ADNP-related Neurodevelopmental Disorders Using Genetic, Medical, and Neuropsychological Measures.
ADNP, Helsmoortel-Van Der Aa Syndrome
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. This study is not recruiting at the moment.
Alexander Kolevzon, MD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ketamine in people with ADNP Syndrome, run by Alexander Kolevzon at 1 site in United States.
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 8 inclusion and 11 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: finished, as of the sponsor's last update on 7 Jul 2023. 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 United States. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With an Adverse Event (time frame: Week 4). 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 7 Jul 2023.