Developing Brain, Impulsivity and Compulsivity

Attention Deficit Hyperactivity Disorder Clinical Trial

Official title:

An Observational Study of the Developing Brain, Impulsivity and Compulsivity.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04631042
• Other study ID #: 200147
• Secondary ID: 20-HG-0147
• Status: Recruiting
• Start date: September 30, 2022
• Est. completion date: December 31, 2031

Study information

• Verified date: June 12, 2023
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Wendy S Sharp, L.C.S.W.
• Phone: (301) 496-0851
• Email: sharpw[@]mail.nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background: Impulsivity is acting 'without thinking.' Compulsivity is being overly inflexible. People vary in how impulsive or compulsive they are. Extreme versions of these behaviors play a role in mental disorders. Researchers want to study changes in the brain to learn more about these behaviors. Differences in genes may also play a role. Objective: To learn about genetic and brain features that explain why levels of impulsivity and compulsivity vary across people. Eligibility: People ages 6-80 Design: Participants will be screened with a medical history and medical record review. Participants will talk about their mental and behavioral development. They may discuss topics like drug use and sexual activity. They will complete surveys about their compulsivity and impulsivity. Parents of child participants may also complete these surveys. Participants may take memory, attention, and thinking tests. They may give blood or saliva samples for gene studies. Participants may have a magnetic resonance imaging scan. It will take pictures of their brain. The scanner is shaped like a cylinder. Participants will lie on a table that slides in and out of the scanner. A coil will be placed over their head. They will lie still, watch a movie, and play a game. Participants may have a magnetoencephalography scan. It records brain activity. Participants will sit in a room. A 'cone' of magnetic field detectors will be lowered around their head. They will rest and play a game. Participants may ask family members to join the study. Participants under age 25 may repeat these tests every 1-2 years until they turn 25 or until the study ends. For those over age 25, participation will last less than 1 month.

Description:

Study Description: Many neuropsychiatric disorders have extreme impairing impulsivity and compulsivity behaviors at their core. We hypothesized that the development of symptoms of impulsivity and compulsivity during childhood/adolescence and early adulthood will be associated with atypical trajectories of brain features including cortical glutamate (the main excitatory neurotransmitter) and functional/structural brain connectivity. Additionally, we hypothesize that cortical glutamate will be under genetic control (i.e., heritable) and that common genetic variant risk for disorders characterized by extreme impulsivity (e.g., attention deficit hyperactivity disorder) and by extreme compulsivity (e.g., obsessive compulsive disorder) will also be associated with atypical cortical glutamate trajectories. To elucidate the relationships between the developing brain, compulsivity/impulsivity and genomics, we will collect clinical assessments including clinician-led interviews, neurobehavioral assessments, neuroimaging data, and genomic samples using 1) a prospective longitudinal design to answer developmental hypotheses; 2) an extended multigenerational family design to assess genomic hypotheses. Objectives: Primary Objectives: A) To assess the effects of impulsivity and compulsivity on the developmental trajectories of cortical glutamate. B) To determine the heritability of cortical glutamate. Secondary Objectives: A) To establish the reliability of glutamate measurements. B) To examine the impact of atypical glutamate levels on developing structural and functional connections within the fronto-striatal circuits. Endpoints: Primary Endpoint: A) Age-related change in cortical glutamate levels and its moderation by individual differences in levels of impulsivity and compulsivity. B) Heritability of cortical glutamate (proportion of variance explained by additive genetic factors). Secondary Endpoints: A) 1. Glutamate levels estimated at 3 Tesla at short intervals to establish test-retest reliability. 2. Glutamate levels estimated at both 3 Tesla and 7 Tesla (cross scanner validation). B) Measures of the brain s structural and functional connectivity. Study Population: We aim to recruit 1100 participants over the next 7 years. Individuals between 6 and 80 years of age with a wide range of impulsivity/compulsivity behaviors - ranging from normal to mildly/extremely impaired - will be recruited. No specific demographic groups will be targeted. Recruitment will be mainly done in the District of Columbia/Maryland/Virginia area, however some participants needed for primary aim B (heritability) might travel from elsewhere. Description of Sites/Facilities Enrolling Participants: The National Institute of Health is the sole site for enrollment of participant. Study Duration: The estimated study duration from the beginning of the study (study opens to enrollment) to the end (completion of data analyses) is 10 years. Participant Duration: Primary Objective A: Participants may complete follow-up visits for as long as the study is open; thus, they might complete visits over a 7 to 10-year period. Primary Objective B: Participants will complete the study after one visit and may complete forms at home; thus, the estimated time for participation is less than a month.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1100
• Est. completion date: December 31, 2031
• Est. primary completion date: December 31, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 80 Years

Eligibility

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the

following criteria:

1. Stated willingness to comply with all study procedures and availability for the duration of the study.

2. Male or female, 6 years of age and under 80 years of age.

3. Ability of participant to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation

in this study:

1. Cognitively not capable of performing study procedures or lack of capacity to provide informed consent. Indications of a lack of cognitive capacity could include a known full-scale IQ under 70, or a history from the screening interview that implies global intellectual disabilities (e.g., placement in a school for children with intellectual disability etc.)

2. Very premature birth (i.e., birth before 32 weeks of gestational age).

3. Any known brain abnormalities (e.g., tumor, periventricular leukomalacia, microcephaly) or history of medical conditions known to affect cerebral anatomy (e.g., epilepsy, history of stroke, head injury with a loss of consciousness of one hour or more).

4. Psychotic disorders (including schizophrenia, psychosis not otherwise specified).

5. Dementia, or other conditions that, in the opinion of the investigators, would impede compliance or possibly hinder completion of the study.

6. Pregnant women.

Additional exclusion criteria for optional MRI procedure:

1. Individuals who are not able to receive an MRI (e.g., metal bioimplants, claustrophobia, inability to lie flat on their backs, pregnant women, and any other contraindications for MRI scanning according to the NMR Center MRI safety guidelines).

2. Medications that are known to affect glutamate levels (e.g., riluzole, memantine, C- cycloserine).

3. Antipsychotic medication (as these have a major impact on dopamine levels).

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder
• Conduct Disorder
• Impulsive Behavior
• Obsessive Compulsive Disorder
• Obsessive-Compulsive Disorder
• Typical Development

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Human Genome Research Institute (NHGRI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Fineberg NA, Chamberlain SR, Goudriaan AE, Stein DJ, Vanderschuren LJ, Gillan CM, Shekar S, Gorwood PA, Voon V, Morein-Zamir S, Denys D, Sahakian BJ, Moeller FG, Robbins TW, Potenza MN. New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity. CNS Spectr. 2014 Feb;19(1):69-89. doi: 10.1017/S1092852913000801. — View Citation

Naaijen J, Lythgoe DJ, Amiri H, Buitelaar JK, Glennon JC. Fronto-striatal glutamatergic compounds in compulsive and impulsive syndromes: a review of magnetic resonance spectroscopy studies. Neurosci Biobehav Rev. 2015 May;52:74-88. doi: 10.1016/j.neubiorev.2015.02.009. Epub 2015 Feb 21. — View Citation

Ziegler G, Hauser TU, Moutoussis M, Bullmore ET, Goodyer IM, Fonagy P, Jones PB; NSPN Consortium; Lindenberger U, Dolan RJ. Compulsivity and impulsivity traits linked to attenuated developmental frontostriatal myelination trajectories. Nat Neurosci. 2019 Jun;22(6):992-999. doi: 10.1038/s41593-019-0394-3. Epub 2019 May 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glutamate concentration measured using Magnetic Resonance Spectroscopy	Age-related change in cortical glutamate levels and its moderation by individual differences in levels of impulsivity and compulsivity.	Yearly if possible
Primary	Heritability of cortical glutamate (proportion of variance explained by additive genetic factors).	Degree to which glutamate levels are under genetic control.	Baseline
Secondary	Glutamate levels	Glutamate measurement at 7 Tesla is now the gold standard for glutamate measurements, against which we will compare measurements at 3 Tesla.	weeks to months
Secondary	Structural and functional connectivity	Structural and functional connectivity measured throughout development using Magnetic Resonance Imaging and Magnetoencephalography.	Yearly if possible

External Links

•   NIH Clinical Center Detailed Web Page