Assessment of Neural Oscillations in Adult Subjects With Down Syndrome and Typically Developing Subjects in Resting State and While Conducting Cognitive Tasks

NCT ID: NCT04791124

Last Updated: 2021-03-10

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 48 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-01-11
• Study Completion Date: 2021-06-01

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).

Conditions

Down Syndrome

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Typical Developing Subjects

EEG evaluation of typical developing subjects

Electroencephalography

Intervention Type: OTHER

EEG 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

Down Syndrome Subjects

EEG evaluation of DS subjects

Electroencephalography

Intervention Type: OTHER

EEG 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

Interventions

Electroencephalography

EEG 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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Weight ≥ 50 kg and ≤ 100 kg
• Body mass index (BMI) ≥ 18.5 and ≤ 30

• 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.

• 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.

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.

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Aelis Farma

INDUSTRY

Sponsor Role: collaborator

Starlab

UNKNOWN

Sponsor Role: collaborator

Parc de Salut Mar

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rafael de la Torre Fornell, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

IMIM (Hospital del Mar Medical Research Institute)

Locations

IMIM (Hospital del Mar Medical Research Institute)

Barcelona, , Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Rafael de la Torre Fornell, PharmD, PhD

Role: CONTACT

rtorre@imim.es

+34 933 160 484

Ana M Aldea Perona, MD, PhD

Role: CONTACT

aaldea@imim.es

+34 933 160 490

Facility Contacts

Ana M. Aldea Perona, MD, PhD

Role: primary

aaldea@imim.es

+34 933 160 490

Other Identifiers

IMIMFTCL_EEGDS

Identifier Type: -

Identifier Source: org_study_id