Familial Alcoholism Vulnerability Clinical Trial
Official title:
Functional Neuroimaging of Alcoholism Vulnerability: Probing Glutamate and Reward, Using the mGluR5 Inhibitor Mavoglurant
The purpose of this study is to evaluate the role of Mavoglurant in clarifying the neurobiology of alcoholism risk. This is a one-site, randomized, within subjects, counterbalanced double-blind study of a single dose (200mg) of Mavoglurant and placebo.
Status | Recruiting |
Enrollment | 80 |
Est. completion date | June 30, 2025 |
Est. primary completion date | June 30, 2025 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 45 Years |
Eligibility | Inclusion Criteria: - Ages 18-45 years - Estimated full-scale IQ>70 - Individual can cooperate with all study procedures - No history of neurological disorder (e.g., epilepsy) - No major medical condition (e.g., cancer) - No history of significant head trauma - Stable medication treatment 6 weeks prior to study enrollment - Negative urine drug and breathe alcohol test at time of MRI scan - Negative urine pregnancy test at time of MRI scan - No MR contra-indications (e.g., in-body metal implant, severe claustrophobia) - No contra-indications to study drug Exclusion Criteria: - A diagnosis of any psychotic disorder, or current mood or anxiety disorders under DSM-V, using the SCID-V-RV psychiatric interview - A current diagnosis of: a) Alcohol use disorder, if severe (AUD, mild or moderate OK if no craving, tolerance, and withdrawal 3 months prior to interview) b) Substance use disorder - Report of psychotic disorder in a 1ยบ relative - Auditory or visual impairment that interferes with test-taking - Prenatal exposure to alcohol plus currently meeting criteria for features of fetal alcohol syndrome - Not speaking English fluently or being a non-native English speaker, or being educated in a primary language other than English > grade 1 - Intellectual Disability (Full Scale IQ<70) - Traumatic brain injury with loss of consciousness > 30 minutes or concussion in last 30 days - Presence or history of neurosurgery or any neurologic illness that may affect brain physiology (e.g., epilepsy, Multiple Sclerosis), including focal brain lesion seen on structural MRI (all structural scans are read by a board certified radiologist) - A current major medical condition (e.g. cancer, heart failure) - Current pregnancy (all females will be tested with urine screens on the day of MRI) - Women not on an effective form of birth control/contraception or abstinent during time of study visits to prevent exposure of the investigational drug to suspected fetus - Current substance use with the exception of marijuana (THC), provided last use of THC was 24+ hours before visit (All participants will receive a urine screen for the presence of marijuana, cocaine, opiates and a breath screen to detect the presence of alcohol) - Inability to comprehend the consent form appropriately - Inability to cooperate with study procedures - Other specific fMRI exclusions include metal devices, clips or fragments in body (orbital xray performed if needed) |
Country | Name | City | State |
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United States | Hartford Hospital | Hartford | Connecticut |
Lead Sponsor | Collaborator |
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Yale University | National Institute on Alcohol Abuse and Alcoholism (NIAAA) |
United States,
Type | Measure | Description | Time frame | Safety issue |
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Primary | Change in Nucleus accumbens (Nacc)/Ventral striatum (VS) BOLD activation during A1 phase in FHP on study medication vs. placebo | Changes in NAcc/VS BOLD (Blood-oxygen-level-dependent) activation during the A1 loss anticipation prospect phase of the MRI Monetary Incentive Delay task in FHP while on mavoglurant compared to placebo | Mavoglurant and Placebo administration are 1 week apart | |
Primary | BOLD activation to alcohol vs. non-alcohol stimuli during ACR task alcohol versus non-alcohol stimuli | Changes in BOLD response in FHP to alcohol versus non-alcohol stimuli in several brain clusters containing MFC, caudate, parahippocampal gyrus, temporal cortex and cerebellum, when administered mavoglurant compared to placebo | Mavoglurant and Placebo administration are 1 week apart | |
Secondary | Dynamic Causal Modeling (DCM)-determined relationships between nucleus accumbens (NAcc) and -medial PFC BOLD signal during MSDM task | Dynamic Causal Modeling (DCM)-determined relationships between nucleus accumbens (NAcc) and -medial PFC BOLD signal during MSDM fMRI task in FHP while on mavoglurant compared to placebo | Mavoglurant and Placebo administration are 1 week apart | |
Secondary | Regional differences in BOLD signal | Impairment of top down inhibitory control and related cortical activation of the executive control network in FHP while on mavoglurant compared to placebo measured by regional differences in BOLD signaling | Mavoglurant and Placebo administration are 1 week apart |
Status | Clinical Trial | Phase | |
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Completed |
NCT03341715 -
Metabotropic Glutamate Receptor-5 (mGlur5) Effects on Reward-Related fMRI-BOLD Activation in FHP and FHN
|
Early Phase 1 |