Down SyndromeEEGDSNCT04791124
Assessment of Neural Oscillations in Adult Subjects With Down Syndrome and Typically Developing Subjects in Resting State and While Conducting Cognitive Tasks
An observational study of Down Syndrome, run by Parc de Salut Mar at 1 site in Spain.
Trial summary
Background: It has been proposed that a hyperactivity of the endocannabinoids system could be involved in the cognitive deficits involved in Down Syndrome (DS). Hyperactivation of the type-1 cannabinoid (CB1) receptor by exogenous cannabinoids, such as the active principle of cannabis tetrahydrocannabinol (THC)… Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Down Syndrome
- What is being tested?
- Electroencephalography
- How many people
- 48 participants
- Where
- 1 siteSpain
- Study dates
- 11 Jan 2021to 1 Jun 2021
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: A total of 24 healthy subjects (12 male and 12 female) with a range age ≥ 18 and ≤ 35 years will be recruited from the typical developing population. A total of 24 healthy subjects (12 male and 12 female) with Down syndrome with a range age ≥ 18 and ≤ 35 years will be recruited.
Common Inclusion Criteria:
- Weight ≥ 50 kg and ≤ 100 kg
- Body mass index (BMI) ≥ 18.5 and ≤ 30
TD group additional Inclusion Criteria:
- Abstinence for alcohol 72h prior to the screening
- Able to read Spanish and adhere to study requirements.
- Signed informed consent prior to any study-mandated procedure.
DS group additional Inclusion Criteria:
- Clinical diagnosis of Down syndrome (full trisomy 21 and translocations) documented by chromosomal analysis (karyotyping).
- Subject understands and accepts the trial procedures.
- Subject assenting and/or willing to participate.
- Signed informed consent by subject and legal representative prior to any study-mandated procedure.
- Subject independently mobile and have sufficient vision and hearing to participate in study evaluations.
- Abstinence for alcohol 72h prior to the screening.
- Clinical Evaluation of Language Fundamentals Preschool-2 (CELF Preschool-2) test score ≥ 7.
- Subjects must have a parent, or other reliable caregiver who agrees to accompany the subject to all clinic visits, provide information about the subject as required by the protocol, and ensure compliance with study tests.
- Subjects are expected to complete all procedures scheduled during the study visits. They must be able to be understood most of the time and must not use other forms of communication, signs, symbol boards or devices as their primary form of communication.
TD group Exclusion Criteria:
- Substance use disorders except for mild alcohol use disorder and/or mild or moderate nicotine use disorder.
- Testing positive for drugs of abuse in urine at screening or the observation day.
- Lifetime clinically significant cardiovascular, renal, pulmonary, hepatic, onco-hematological, endocrine, gastrointestinal, mental or neurological disease.
- Any other diseases or conditions that in the judgment of the investigator would interfere with the subject's ability to comply with study procedures or requirements and/or study results interpretation.
- Any clinically significant findings in physical examination including vital signs.
- Any prescription or over the counter drug (except occasional use of paracetamol) in the last 2 weeks before Day 1 of each period.
- Patient included in a clinical study with drugs in the last three months.
DS group Exclusion Criteria:
- Mosaic Down syndrome
- Personal history of infantile spasms/convulsions/epilepsy, severe head trauma or central nervous system infections (e.g. meningitis), with the exception of a single isolated febrile seizure.
- Subjects with a current Diagnostic of autism spectrum disorder or any primary psychiatric diagnosis. Diagnoses that are secondary, such as attention deficit hyperactivity disorder, depressive disorders and conduct disorders are allowed as long as they are considered to not interfere with study conduct and are stable during the 3 months preceding randomization. Related allowed treatments must be on stable dosing for the last 3 months.
- Symptoms of early dementia as assessed by the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities.
- Substance use disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria.
- Positive urine test for drugs of abuse or alcohol breath test at screening and prior to dosing.
- Epileptiform abnormalities (excluding isolated sharp waves and beyond those expected for age) in 10 min EEG.
- Any life-threatening disease.
- Any other clinically relevant concomitant disease or condition or finding at screening that in the judgment of the investigator could interfere with, the treatment thereof might interfere with, the conduct of the study and related procedures and/or might bias the study results interpretation, or could jeopardize the subject's safety.
- Neuroleptic drugs within 3 months prior to randomization.
- Any clinically significant findings in physical examination including vital signs.
- Any new prescription or over the counter drug (except occasional use of paracetamol) in the last 2 weeks before Day 1 of each period.
- Testing positive for drugs of abuse in urine at screening or the observation day
- Patient included in a clinical study with drugs in the last three months.
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
IMIM (Hospital del Mar Medical Research Institute)
Barcelona, 08003
Ana M. Aldea Perona, MD, PhD, +34 933 160 490, aaldea@imim.es
Rafael de la Torre Fornell, PharmD, PhD
About this study
Background:
It has been proposed that a hyperactivity of the endocannabinoids system could be involved in the cognitive deficits involved in Down Syndrome (DS). Hyperactivation of the type-1 cannabinoid (CB1) receptor by exogenous cannabinoids, such as the active principle of cannabis tetrahydrocannabinol (THC), induces several modifications of the electroencephalogram (EEG).
Read more
The goal of this study is to compare those CB1-dependent EEG parameters in subjects with DS and age-matched typically developing subjects (TD, control group). These investigations can increase our knowledge of the involvement of the CB1 receptor in DS cognitive deficits and potentially identify biomarkers of target engagement of new therapies of this condition.
Hypothesis:
It was recently showed in pre-clinical DS models that the endocannabinoid system is hyperactivated in the brain and that human adult subjects with DS showed higher plasma concentrations of the main endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (N-arachidonoylethanolamine, 2-AEA) as compared with those found in typically developing subjects. Alterations of neural oscillations induced by the consumption of THC preparations are well established and it is hypothesized that they would be similar to those found in subjects with DS.
Objectives:
To assess different neural markers using electroencephalography (EEG) in typically developing subjects and in subjects with DS in resting state and while conducting selected cognitive tasks.
Methods:
Non-interventional, cross-sectional, monocenter study in male and female adult subjects with DS and typically developing subjects (total n=48).
- Conditions
- Down Syndrome
- Being tested
- Electroencephalography
- Keywords
- Down Syndrome, Electroencephalography, Neural oscillations, Endocannabinoids, Gamma Intertrial Coherence
- Medical subject headings
- Down Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElectroencephalographyOther
EEG evaluation Composed by three consecutive tests
- Resting state EEG, with either eyes open or closed
- Auditory steady-state response (ASSR)
- Auditory evoked potential
| Study group | Role | What they receive |
|---|---|---|
| Typical Developing Subjects | EEG evaluation of typical developing subjects Receives: Other: Electroencephalography | |
| Down Syndrome Subjects | EEG evaluation of DS subjects Receives: Other: Electroencephalography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences in gamma intertrial coherence and power between DS and TD group
Variations in gamma intertrial coherence (ITC) and power during an auditory steady-state response (ASSR) at 40Hz in DS compared to TD subjects.
Measured: During EEG
Differences in power of neural oscillations between DS and TD group
Variations in power of neural oscillations in resting state eyes-closed EEG (alpha, delta, theta, beta, gamma) in DS compared to TD subjects.
Measured: During resting state eyes-closed EEG
Differences in amplitude and latency of various EEG waves between DS and TD group
Variations in amplitude and latency of the P300a and P300b, P300, N100 and N200 waves assessed by a three-stimulus auditory oddball task in DS compared to TD subjects.
Measured: During EEG while performing a three-stimulus auditory oddball task
Differences in EEG complexity between DS and TD group
Variations in EEG complexity measured by the Lempel-Ziv complexity in DS compared to TD subjects.
Measured: During EEG
Differences in EEG brain connectivity, interhemispheric and frontoparietal connectivity, characteristic path and clustering coefficient between DS and TD group
Variations in EEG brain connectivity, interhemispheric and frontoparietal connectivity (measured by band coherence, synchronicity likelihood, phase lag index), characteristic path and clustering coefficient (band coherence, synchronicity likelihood) in resting state (eyes-closed/open) in resting state eyes-closed/open EEG in DS compared to TD subjects.
Measured: During resting state eyes-closed and eyes-open EEG
Differences in cross-frequency coupling between DS and TD group
Variations in cross-frequency coupling (theta-gamma coupling) during the resting state, the auditory and the cognitive tasks in DS compared to TD subjects.
Measured: During resting state EEG, and while performing the auditory and the cognitive tasks
Differences in Higuchi fractal dimension, small-world, characteristic path, and clustering coefficient between DS and TD group
Variations in Higuchi fractal dimension, small-world, characteristic path, and clustering coefficient in DS compared to TD subjects.
Measured: During resting state eyes-closed and eyes-open EEG
Differences in plasma concentrations of endocannabinoids between DS and TD group
Variations in plasma concentrations of endocannabinoids (AEA and 2AG) in DS compared to TD subjects.
Measured: At baseline
Differences in plasma concentrations of the neurosteroid pregnenolone between DS and TD group
Variations in plasma concentrations of the neurosteroid pregnenolone in DS compared to TD subjects.
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2021
- Study start11 Jan 2021
- Primary completion1 Jun 2021 (estimated)
- Study completion1 Jun 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Down 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 48 participants (estimated)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- Parc de Salut Mar
- Sponsor type
- University, hospital or other
- Collaborators
- Aelis Farma, Starlab
- Responsible party
- Sponsor
- Investigators
- Rafael de la Torre Fornell, PharmD, PhD, Principal investigator, IMIM (Hospital del Mar Medical Research Institute)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04791124
- Sponsor's protocol ID
- IMIMFTCL_EEGDS
- Acronym
- EEGDS
- Status last verified
- Mar 2021
- First submitted
- 5 Mar 2021
- Last updated
- 10 Mar 2021
- 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 10 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Neural Oscillations in Adult Subjects With Down Syndrome and Typically Developing Subjects in Resting State and While Conducting Cognitive Tasks
- ClinicalTrials.gov ID
- NCT04791124
- Acronym / sponsor ID
- EEGDS / IMIMFTCL_EEGDS
- Conditions
- Down Syndrome
- Keywords
- Down Syndrome, Electroencephalography, Neural oscillations, Endocannabinoids, Gamma Intertrial Coherence
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Parc de Salut MarUniversity, hospital or other
- Collaborators
- Aelis Farma, Starlab
- Study start
- 11 Jan 2021 (actual)
- Primary completion
- 1 Jun 2021 (estimated)
- Study completion
- 1 Jun 2021 (estimated)
- First posted
- 10 Mar 2021 (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.
Background:
It has been proposed that a hyperactivity of the endocannabinoids system could be involved in the cognitive deficits involved in Down Syndrome (DS). Hyperactivation of the type-1 cannabinoid (CB1) receptor by exogenous cannabinoids, such as the active principle of cannabis tetrahydrocannabinol (THC), induces several modifications of the electroencephalogram (EEG).
The goal of this study is to compare those CB1-dependent EEG parameters in subjects with DS and age-matched typically developing subjects (TD, control group). These investigations can increase our knowledge of the involvement of the CB1 receptor in DS cognitive deficits and potentially identify biomarkers of target engagement of new therapies of this condition.
Hypothesis:
It was recently showed in pre-clinical DS models that the endocannabinoid system is hyperactivated in the brain and that human adult subjects with DS showed higher plasma concentrations of the main endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (N-arachidonoylethanolamine, 2-AEA) as compared with those found in typically developing subjects. Alterations of neural oscillations induced by the consumption of THC preparations are well established and it is hypothesized that they would be similar to those found in subjects with DS.
Objectives:
To assess different neural markers using electroencephalography (EEG) in typically developing subjects and in subjects with DS in resting state and while conducting selected cognitive tasks.
Methods:
Non-interventional, cross-sectional, monocenter study in male and female adult subjects with DS and typically developing subjects (total n=48).
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Target follow-up
- 1 Day
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Typical Developing Subjects | – | Other: ElectroencephalographyEEG evaluation of typical developing subjects |
| Down Syndrome Subjects | – | Other: ElectroencephalographyEEG evaluation of DS subjects |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- A total of 24 healthy subjects (12 male and 12 female) with a range age ≥ 18 and ≤ 35 years will be recruited from the typical developing population. A total of 24 healthy subjects (12 male and 12 female) with Down syndrome with a range age ≥ 18 and ≤ 35 years will be recruited.
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 |
|---|---|---|
| ElectroencephalographyEEG evaluation Composed by three consecutive tests 1. Resting state EEG, with either eyes open or closed 2. Auditory steady-state response (ASSR) 3. Auditory evoked potential | Other | Down Syndrome Subjects, Typical Developing Subjects |
Primary outcome
Differences in gamma intertrial coherence and power between DS and TD group
Time frame: During EEG
Variations in gamma intertrial coherence (ITC) and power during an auditory steady-state response (ASSR) at 40Hz in DS compared to TD subjects.
Differences in power of neural oscillations between DS and TD group
Time frame: During resting state eyes-closed EEG
Variations in power of neural oscillations in resting state eyes-closed EEG (alpha, delta, theta, beta, gamma) in DS compared to TD subjects.
Differences in amplitude and latency of various EEG waves between DS and TD group
Time frame: During EEG while performing a three-stimulus auditory oddball task
Variations in amplitude and latency of the P300a and P300b, P300, N100 and N200 waves assessed by a three-stimulus auditory oddball task in DS compared to TD subjects.
Differences in EEG complexity between DS and TD group
Time frame: During EEG
Variations in EEG complexity measured by the Lempel-Ziv complexity in DS compared to TD subjects.
Differences in EEG brain connectivity, interhemispheric and frontoparietal connectivity, characteristic path and clustering coefficient between DS and TD group
Time frame: During resting state eyes-closed and eyes-open EEG
Variations in EEG brain connectivity, interhemispheric and frontoparietal connectivity (measured by band coherence, synchronicity likelihood, phase lag index), characteristic path and clustering coefficient (band coherence, synchronicity likelihood) in resting state (eyes-closed/open) in resting state eyes-closed/open EEG in DS compared to TD subjects.
Differences in cross-frequency coupling between DS and TD group
Time frame: During resting state EEG, and while performing the auditory and the cognitive tasks
Variations in cross-frequency coupling (theta-gamma coupling) during the resting state, the auditory and the cognitive tasks in DS compared to TD subjects.
Differences in Higuchi fractal dimension, small-world, characteristic path, and clustering coefficient between DS and TD group
Time frame: During resting state eyes-closed and eyes-open EEG
Variations in Higuchi fractal dimension, small-world, characteristic path, and clustering coefficient in DS compared to TD subjects.
Differences in plasma concentrations of endocannabinoids between DS and TD group
Time frame: At baseline
Variations in plasma concentrations of endocannabinoids (AEA and 2AG) in DS compared to TD subjects.
Differences in plasma concentrations of the neurosteroid pregnenolone between DS and TD group
Time frame: At baseline
Variations in plasma concentrations of the neurosteroid pregnenolone in DS compared to TD subjects.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2021.
- 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. This study is not recruiting at the moment.
Rafael de la Torre Fornell, PharmD, PhD principal investigator
IMIM (Hospital del Mar Medical Research Institute)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Down Syndrome, run by Parc de Salut Mar at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: status not confirmed, as of the sponsor's last update on 10 Mar 2021. 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 Spain. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rafael de la Torre Fornell, PharmD, PhD (+34 933 160 484, rtorre@imim.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in gamma intertrial coherence and power between DS and TD group (time frame: During EEG). The study lists 9 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 10 Mar 2021.