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NCT Number: NCT07076342

The Role of mGluR5 in CBT-I

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.

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Key information

Conditions

Major Depressive Disorder (MDD) Depressive Disorder Depressive Disorder, Major Dyssomnias Mental Disorders Mood Disorders Nervous System Diseases Sleep Disorders, Intrinsic Sleep Initiation and Maintenance Disorders Sleep Wake Disorders

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Stony Brook University: Dept of Psychiatry

Stony Brook, New York, 11794, United States

Location status: Recruiting

Location contact

Christine DeLorenzo, PhD

CONTACT

[email protected]

(631) 638-1523

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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)

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.

Primary outcomes

  1. Change in Sleep Latency from Baseline to 8 Weeks

    Time frame: Baseline and 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.

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

    Time frame: Baseline and 8 weeks

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Christine DeLorenzo, PhD

CONTACT

[email protected]

(631) 638-1523

Wendy Zhang

CONTACT

[email protected]

(631)-638-2053

Sponsors and collaborators

Lead sponsor

Stony Brook University

Other

Collaborators

  • National Institute of Mental Health (NIMH)
  • National Institutes of Health (NIH)

Registry information

Official study title

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)

Important dates

Study start
2025
Primary completion
2030
Study completion
2030
First posted
Jul 22, 2025
Registry last updated
Feb 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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