Clinical trial NCT04791124: Assessment of Neural Oscillations in Adult Subjects With Down Syndrome and Typically Developing Subjects in Resting State and While Conducting Cognitive Tasks
Official title: Assessment of Neural Oscillations in Adult Subjects With Down Syndrome and Typically Developing Subjects in Resting State and While Conducting Cognitive Tasks
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Down Syndrome
Keywords: Down Syndrome
Electroencephalography
Neural oscillations
Endocannabinoids
Gamma Intertrial Coherence
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
Collaborators: name: Aelis Farma
name: Starlab
First posted: 2021-03-10
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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), 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Differences in gamma intertrial coherence and power between DS and TD group
timeFrame: During EEG
measure: Differences in power of neural oscillations between DS and TD group
timeFrame: During resting state eyes-closed EEG
measure: Differences in amplitude and latency of various EEG waves between DS and TD group
timeFrame: During EEG while performing a three-stimulus auditory oddball task
measure: Differences in EEG complexity between DS and TD group
timeFrame: During EEG
measure: Differences in EEG brain connectivity, interhemispheric and frontoparietal connectivity, characteristic path and clustering coefficient between DS and TD group
timeFrame: During resting state eyes-closed and eyes-open EEG
measure: Differences in cross-frequency coupling between DS and TD group
timeFrame: During resting state EEG, and while performing the auditory and the cognitive tasks
measure: Differences in Higuchi fractal dimension, small-world, characteristic path, and clustering coefficient between DS and TD group
timeFrame: During resting state eyes-closed and eyes-open EEG
measure: Differences in plasma concentrations of endocannabinoids between DS and TD group
timeFrame: At baseline
measure: Differences in plasma concentrations of the neurosteroid pregnenolone between DS and TD group
timeFrame: At baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: IMIM (Hospital del Mar Medical Research Institute)
Study officials:
affiliation: IMIM (Hospital del Mar Medical Research Institute)
name: Rafael de la Torre Fornell, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
References: