Major Depressive Disorder (MDD)Phase 4NCT07076342
The Role of mGluR5 in CBT-I
A Phase 4 study testing Cognitive Behavioral Therapy for Insomnia and PET Scan with [11C]ABP688 in people with Major Depressive Disorder (MDD), run by Stony Brook University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Major Depressive Disorder (MDD)
- What is being tested?
- Cognitive Behavioral Therapy for Insomnia and PET Scan with [11C]ABP688
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2025to 31 Mar 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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,
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Stony Brook University: Dept of Psychiatry
Stony Brook, New York, 11794
Christine DeLorenzo, PhD, (631) 638-1523, Christine.DeLorenzo@stonybrookmedicine.edu
About this study
Official 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)
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.
Read the 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)
- Being tested
- Cognitive Behavioral Therapy for Insomnia, PET Scan with [11C]ABP688
- Keywords
- Cognitive Behavioral Therapy, CBT-I, Cognitive Behavioral Therapy & Insomnia, Major Depressive Disorder
- Medical subject headings
- Depressive Disorder, Major, Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive Behavioral Therapy for InsomniaBehavioural
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]ABP688Drug
Prior to and after completing the CBT-I protocol, participants will undergo a PET scan using tracer [11C]ABP688) to quantify hippocampal mGluR5 density.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Behavioral: Cognitive Behavioral Therapy for Insomnia; Drug: PET Scan with [11C]ABP688 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline and 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2025
- Study start1 Aug 2025
- Primary completion31 Mar 2030 (estimated)
- Study completion31 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive Disorder (MDD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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").
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stony Brook University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Christine DeLorenzo, Stony Brook University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07076342
- Sponsor's protocol ID
- 2025-00015
- Other IDs
- 1R01MH137211-01A1, 2025
- Status last verified
- Aug 2025
- First submitted
- 14 Jul 2025
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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)
- ClinicalTrials.gov ID
- NCT07076342
- Acronym / sponsor ID
- 2025-00015
- Conditions
- Major Depressive Disorder (MDD)
- Keywords
- Cognitive Behavioral Therapy, CBT-I, Cognitive Behavioral Therapy & Insomnia, Major Depressive Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Stony Brook UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Institute of Mental Health (NIMH)
- Study start
- 1 Aug 2025 (actual)
- Primary completion
- 31 Mar 2030 (estimated)
- Study completion
- 31 Mar 2030 (estimated)
- First posted
- 22 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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").
| Arm | Type | Receives |
|---|---|---|
| Cognitive Behavioral Therapy for Insomnia Treatment Arm | Experimental | Behavioral: Cognitive Behavioral Therapy for Insomnia, Drug: PET Scan with [11C]ABP688Cognitive Behavioral Therapy for Insomnia (CBT-I) will be delivered through an online program, Sleep Healthy Using The Internet (SHUTi). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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),
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive Behavioral Therapy for InsomniaCognitive Behavioral Therapy for Insomnia (CBT-I) will be delivered through an online program, Sleep Healthy Using The Internet Sleep Healthy Using The Internet (SHUTi) | Behavioural | Cognitive Behavioral Therapy for Insomnia Treatment Arm |
| PET Scan with [11C]ABP688Prior to and after completing the CBT-I protocol, participants will undergo a PET scan using tracer [11C]ABP688) to quantify hippocampal mGluR5 density. | Drug | Cognitive Behavioral Therapy for Insomnia Treatment Arm |
Primary outcome
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.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Cognitive Behavioral Therapy for Insomnia and PET Scan with [11C]ABP688 in people with Major Depressive Disorder (MDD), run by Stony Brook University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wendy Zhang ((631)-638-2053, Wendy.Zhang@stonybrookmedicine.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Sleep Latency from Baseline to 8 Weeks (time frame: Baseline and 8 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026.