The Role of mGluR5 in CBT-I

Stony Brook University

Status and phase

Enrolling

Phase 4

Conditions

Major Depressive Disorder (MDD)

Treatments

Drug: PET Scan with [11C]ABP688

Behavioral: Cognitive Behavioral Therapy for Insomnia

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT07076342

1R01MH137211-01A1 (U.S. NIH Grant/Contract)

2025-00015

Details and patient eligibility

About

This is mechanistic clinical trial that evaluates the role of one of the glutamate receptors (mGluR5) in cognitive behavioral therapy for insomnia (CBT-I) as a common pathway in improving sleep and depression.

Full description

Cognitive behavioral therapy for insomnia (CBT-I), a treatment solely aimed at improving sleep, reduces depression with rates similar to conventional antidepressants. Although this efficacy reflects the interrelationship between sleep and depression, CBT-I's antidepressant mechanism of action is currently unknown. One potential mechanistic pathway is through the metabotropic glutamate receptor subtype 5 (mGluR5), due to its strong association with both depression and sleep. The investigators hypothesize that CBT-I's antidepressant efficacy may occur through the downregulation of mGluR5 associated with improved sleep. This study is a mechanistic clinical trial in a cohort of adults with MDD and a range of sleep latencies (time it takes to fall asleep). Prior to and following CBT-I, the investigators will quantify hippocampal mGluR5 density (with using positron emission tomography [PET] imaging) and sleep latency (with polysomnography performed in the Sleep Lab). CBT-I will be delivered through an online program, Sleep Healthy Using The Internet (SHUTi).

Enrollment

42 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

capacity to provide informed consent,
at least 18 years of age
good physical health and absence of significant medical conditions,
diagnosis of major depressive disorder (MDD) with current major depressive episode as per DSM-5 criteria
Montgomery-Åsberg Depression Rating Scale (MADRS) score > 29 (at least moderate depression),
uniform range of sleep latencies up to 128 minutes.

Exclusion criteria

currently taking effective antidepressants,
lifetime history of psychosis,
drug or alcohol dependence in the last 6 months or abuse in the last 2 months
unstable medical condition (i.e., condition not adequately stabilized for ≥ 3 months)
nicotine use within 1 year
currently on medication known to affect glutamate,
sleep disorders, other than insomnia, such as sleep apnea,
recent (within 1 year) regular night shift work (or rotating shift work) or recent (within 3 months) travel across more than one time zone, or plans for this work or travel during the study period,
use of medication or substances that affect sleep, for example, ingestion of more > 600 mg of caffeine per day,
PET or MRI contraindications, including pregnancy or currently breastfeeding