NCT07076342

The Role of mGluR5 in CBT-I

Mechanistic Clinical Trial Evaluating the Role of the Metabotropic Glutamate Receptor Subtype 5 (mGluR5) in the Antidepressant Mechanism of Cognitive Behavioral Therapy for Insomnia (CBT-I)

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: Stony Brook University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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).

Conditions

• Major Depressive Disorder (MDD)

Interventions

Type	Name	Description
BEHAVIORAL	Cognitive Behavioral Therapy for Insomnia	Cognitive Behavioral Therapy for Insomnia (CBT-I) will be delivered through an online program, Sleep Healthy Using The Internet Sleep Healthy Using The Internet (SHUTi)
DRUG	PET Scan with [11C]ABP688	Prior to and after completing the CBT-I protocol, participants will undergo a PET scan using tracer \[11C\]ABP688) to quantify hippocampal mGluR5 density.

Timeline

• Start date: 2025-08-01
• Primary completion: 2030-03-31
• Completion: 2030-03-31
• First posted: 2025-07-22
• Last updated: 2026-02-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study