The Role of mGluR5 in CBT-I

NCT07076342 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 2025-000151R01MH137211-01A1
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Major Depressive Disorder (MDD)

Keywords

Cognitive Behavioral Therapy; CBT-I; Cognitive Behavioral Therapy & Insomnia; Major Depressive Disorder

Outcome Measures

Primary Outcomes (2)

• Change in Sleep Latency from Baseline to 8 Weeks

  Polysomnography: Prior to and following CBT-I, participants will spend one or two nights in the facility's Sleep Lab in order to assess sleep latency (i.e., quantity of sleep). While the participant sleeps, polysomnography, including EEG will be collected. This will be used to quantify sleep latency.

  Baseline and 8 Weeks

• Change from Baseline of mGluR5 density in the hippocampus after 8 weeks of CBT-I Treatment

  PET Imaging: Prior to and following CBT-I, participants will receive PET imaging to allow measurement of change in mGluR5 (a protein receptor in the brain) density in the hippocampus.

  Baseline and 8 weeks

Study Arms (1)

Cognitive Behavioral Therapy for Insomnia Treatment Arm

EXPERIMENTAL

Cognitive Behavioral Therapy for Insomnia (CBT-I) will be delivered through an online program, Sleep Healthy Using The Internet (SHUTi).

Behavioral: Cognitive Behavioral Therapy for Insomnia; Drug: PET Scan with [11C]ABP688

Interventions

Cognitive Behavioral Therapy for Insomnia BEHAVIORAL

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)

Cognitive Behavioral Therapy for Insomnia Treatment Arm

PET Scan with [11C]ABP688 DRUG

Prior to and after completing the CBT-I protocol, participants will undergo a PET scan using tracer \[11C\]ABP688) to quantify hippocampal mGluR5 density.

Cognitive Behavioral Therapy for Insomnia Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Stony Brook University: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Stony Brook University: Dept of Psychiatry

Stony Brook, New York, 11794, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Sleep Initiation and Maintenance Disorders

Interventions

Cognitive Behavioral Therapy; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Central Study Contacts

Wendy Zhang

CONTACT

(631)-638-2053; Wendy.Zhang@stonybrookmedicine.edu

Christine DeLorenzo, PhD

CONTACT

(631) 638-1523; christine.delorenzo@stonybrookmedicine.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry & Biomedical Engineering, Director (CUBIT)

Model Details: Prior to and following CBT-I, the investigators will quantify hippocampal mGluR5 density (with PET using \[11C\]ABP688) and sleep latency (with polysomnography study performed in a Sleep Lab Facility), CBT-I will be delivered through an online program, Sleep Healthy Using The Internet (SHUTi, pronounced "shut eye").

Study Record Dates

• First Submitted: July 14, 2025
• First Posted: July 22, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): March 31, 2030
• Last Updated: February 17, 2026

Record last verified: 2025-08

Locations

US (1)