Depression; Major Depressive DisorderNCT04350567
Sleep/Wake Cycle and Depression: An Imaging and Treatment Study
A study testing Sleep Deprivation in people with Depression; Major Depressive Disorder, run by Stony Brook University at 1 site in United States.
Trial summary
16.2 million American adults are affected by depression each year. The investigators are studying the relationship between sleep/wake cycle and depression. Mounting evidence suggests that abnormalities in circadian rhythms (biological changes that happen over the course of the day or night) are related to mood… Read more about this study
- Who is it for?
- Ages 18 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Depression; Major Depressive Disorder
- What is being tested?
- Sleep Deprivation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2020to 31 May 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 to 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Participant considered at significant risk for suicide
- Unlikely to tolerate medication washout or the drug free period following washout (depressed participants only)
- Current psychosis
- ECT within 4 weeks of the first overnight visit
- Significant active physical illness or neurological deficit that may affect brain function or imaging
- A disease, job or life circumstance that creates an irregular circadian rhythm anticipated during the study
Show all 16Show fewer
- Inability to maintain in bed and out of bed (regardless of sleep time, for depressed individuals) or sleep and wake times (for non-depressed individuals) to within ~30 min for a week before each overnight visit (will be measured by actigraphy and/or other measurements)
- Inability to abstain from medications that will affect glutamate levels or circadian rhythms, including stimulants, anti-epileptics, antidepressants, beta-blockers, hypnotics (including benzodiazepines), melatonin, or medications with glutamateric or GABAergic modes of action within 4 weeks before the first overnight visit as well as throughout the study
- Inability to reduce caffeine intake to <= ~300 mg of caffeine (~2.5 cups of coffee or equivalents) daily within 4 weeks of the first overnight visit as well as throughout the study
- Inability to abstain from nicotine within 4 weeks before the first overnight visit as well as throughout the study
- Inability to reduce use of alcohol to <= ~5 drinks per week from 4 weeks before the first overnight visit and throughout the study and to completely abstain from alcohol within 24 hours of any overnight visit
- Inability to abstain from significant substance use (including cannabis) within 4 weeks before the first overnight visit as well as throughout the study
- Planned intermittent fasting or calorie restricted diet within 4 weeks before the first overnight visit as well as throughout the study
- For females: Pregnancy within the past year, currently lactating; planning to conceive during the course of study participation, or abortion in the past two months
- Any MRI contraindications, including metal implants, pacemaker, metal prostheses, orthodontic appliances, or presence of shrapnel that are contraindicated for MRI
- Any PET contraindications, including if study imaging will result in the participant receiving greater exposure than the research limit, or if participant is currently breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Stony Brook University Hospital
Stony Brook, New York, 11794
About this study
Official title: Role of the Metabotropic Glutamate Receptor Subtype 5 in Circadian Rhythm Misalignment and Depression: Implications for Treatment
16.2 million American adults are affected by depression each year. The investigators are studying the relationship between sleep/wake cycle and depression. Mounting evidence suggests that abnormalities in circadian rhythms (biological changes that happen over the course of the day or night) are related to mood disorders. This may explain why people with depression frequently suffer with sleeping problems. The purpose of this study is to understand how circadian (sleep/wake) rhythms may be affected in depression and the best way to improve depression caused in this way. This will be performed by comparing circadian (sleep/wake) rhythms in people with and without depression.
The study involves being kept awake for one night. For depressed individuals, this technique will likely result in a brief (<1 day) improvement in depression. Following this study, participants with depression will be offered antidepressant medication at no cost. During the study, the investigators use brain scans to learn more about brain chemistry in health and depression.
Read the detailed description
The study involves four overnight stays, three occurring consecutively and one occurring at a separate timepoint. For the three-night consecutive stay, on Overnight-1, sleep can occur as normal and the investigators will measure hormone levels during sleep. On Overnight-2, participants will be kept awake for around 36 hours. On Overnight-3, the investigators will measure hormone levels again during sleep. During a separately scheduled single overnight session (which happens sometime before or after the three-night consecutive stay), three sets of imaging over the course of the night are performed. The imaging is positron emission tomography (PET). It is designed to look at brain chemistry (particularly glutamate receptors in the brain). Participants may sleep in between scans. All participants with depression enrolled in the study will be seen by a clinician throughout the study and offered medication at no cost after the study.
Aim 1: Assess circadian (sleep/wake) phase in depressed and non-depressed individuals. Melatonin secretion is now an easily accessible circadian marker. Further, the average time interval between dim light melatonin onset (DLMO, the time at which melatonin rises above a certain threshold, "the most accurate biomarker of circadian phase position") and sleep midpoint (average bedtime plus half the average sleep duration) has been established as 6 hours in non-depressed participants and likely deviates from this optimum in major depressive disorder (MDD). For this reason, the investigators will measure melatonin in the blood on overnight visit 1.
Hypothesis 1. Average phase angle difference (DLMO - sleep midpoint) will be 6 hours (optimal) in healthy controls, but not depressed, participants.
Hypothesis 2. MDD severity (assessed by the Hamilton Depression Rating Scale, HDRS) will be correlated with deviation from optimal phase angle difference.
Aim 2: Assess brain chemistry (specifically one of the glutamate receptors, the metabotropic glutamate receptor subtype 5, mGluR5) expression at 3 times: the time of DLMO, peak and nadir of melatonin secretion (as measured from overnight visit 1). mGluR5 availability will be assessed near these times to capture mGluR5 circadian rhythmicity using PET and a tracer specific for mGluR5, [11C]ABP688.
Hypothesis 3. mGluR5 variation will be inverse to that of melatonin in both cohorts.
Aim 3: Determine the effect of acute sleep deprivation on circadian rhythms. Within approximately one week of Aims 1 \& 2, all participants will receive sleep deprivation therapy. Following up to 36 hours of wakefulness (shown to increase mGluR5 at a single time point), the investigators will measure acute effects with repeat assessments of melatonin and depression severity. This will thus require two overnight stays in a row- one for the sleep deprivation and then the next to measure melatonin again in the blood while the participant sleeps.
Hypothesis 4. Sleep deprivation will be most successful in the depressed participants with greatest disruption in phase (Aim 1).
Hypothesis 5: Depressed participants will experience greater changes in phase angle difference following sleep deprivation than non-depressed participants.
Aim 4: To determine whether reliable estimates of [11C]ABP688 in plasma can be obtained using a miniPET scanner. [11C]ABP688 concentration will be measured at the wrist or leg with a novel synchronized PET scanner developed by Stony Brook Investigator, Dr. Paul Vaska. This innovative device provides estimates of plasma radioactivity simply by placing the participant's wrist or leg in a mini-PET scanner called versaPET. The radioactivity derived from this wrist or leg scanner, as well as the resulting outcome measures, will be compared to those estimated using blood analysis. This could make future PET studies easier by finding a substitute for blood sampling during the PET scan.
Uncovering the link between mGluR5, circadian disruption and MDD could:
(1) Identify biological underpinnings of circadian (sleep/wake) dysfunction; (2) Identify individuals (those with mGluR5 disruption) for whom treatments like sleep deprivation would be most effective; and (3) Increase use of this safe and rapid treatment.
- Conditions
- Depression; Major Depressive Disorder
- Being tested
- Sleep Deprivation
- Medical subject headings
- Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sleep DeprivationOther
On the first night, the participant sleeps normally as we assess their melatonin through blood work. On the second night, the participant has 3 PET/MRI scans. On the third night, the participant undergoes sleep deprivation. On the fourth night, the participant sleeps normally and we assess their melatonin again through blood work. Depression scores are taken before and after the intervention.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Not described Receives: Other: Sleep Deprivation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure circadian phase in depressed and non-depressed individuals using the following outcome measure: phase angle difference (DLMO - sleep midpoint, units: hours)
Hypothesis 1. Average phase angle difference (DLMO - sleep midpoint) will be 6 hours (optimal) in non-depressed participants. Hypothesis 2. MDD severity (assessed by the Hamilton Depression Rating Scale, HDRS) will be correlated with deviation from optimal phase angle difference. For this hypothesis, two outcome measures (phase angle difference, in hours) and HDRS (unitless, ranges from 0 to 52, higher numbers indicate worse depression severity) will be combined in the following way: the Pearson correlation coefficient will be assessed between the phase angle difference and HDRS of each individual. The correlation coefficient will be reported, and is expected to be positive.
Measured: 8 Weeks
Secondary outcomes (3)
Measure mGluR5 expression (outcome measure: volume of distribution divided by free fraction) at the time of DLMO, peak and nadir of melatonin secretion.
Hypothesis 3. mGluR5 variation will be inverse to that of melatonin in both cohorts. For this hypothesis, two outcome measures (mGluR5 expression at three time points) and (melatonin level at three time points) will be combined in the following way: the Pearson correlation coefficient will be assessed between mGluR5 expression and melatonin level within each individual. The correlation coefficient will be reported, and is expected to be negative.
Measured: 8 Weeks
Measure the effect of acute sleep deprivation on circadian rhythms (outcome measure: shift of the concentration of melatonin over time curve).
Within approximately one week of Aims 1 \& 2, all participants will receive sleep deprivation therapy. Following up to 36 hours of wakefulness (shown to increase mGluR5 at a single time point), we will measure acute effects with repeat assessments of melatonin. This will require two overnight stays in a row- one for the sleep deprivation and one to measure melatonin again in the blood while the participant sleeps.
Measured: 8 Weeks
To determine whether reliable estimates of [11C]ABP688 in plasma can be obtained using a miniPET scanner.
Outcome measure: sum of square differences between [11C]ABP688 measured in blood samples compared to the concentration measured using the miniPET scanner.
Measured: 8 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2020
- Study start1 Sep 2020
- Primary completion31 May 2025
- Study completion31 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depression; Major Depressive DisorderStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stony Brook University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christine DeLorenzo, Stony Brook University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04350567
- Sponsor's protocol ID
- 1218123
- Status last verified
- May 2025
- First submitted
- 17 Mar 2020
- Last updated
- 17 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of the Metabotropic Glutamate Receptor Subtype 5 in Circadian Rhythm Misalignment and Depression: Implications for Treatment
- ClinicalTrials.gov ID
- NCT04350567
- Acronym / sponsor ID
- 1218123
- Conditions
- Depression; Major Depressive Disorder
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Stony Brook UniversityUniversity, hospital or other
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 31 May 2025 (actual)
- Study completion
- 31 May 2025 (actual)
- First posted
- 17 Apr 2020 (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.
16.2 million American adults are affected by depression each year. The investigators are studying the relationship between sleep/wake cycle and depression. Mounting evidence suggests that abnormalities in circadian rhythms (biological changes that happen over the course of the day or night) are related to mood disorders. This may explain why people with depression frequently suffer with sleeping problems. The purpose of this study is to understand how circadian (sleep/wake) rhythms may be affected in depression and the best way to improve depression caused in this way. This will be performed by comparing circadian (sleep/wake) rhythms in people with and without depression.
The study involves being kept awake for one night. For depressed individuals, this technique will likely result in a brief (<1 day) improvement in depression. Following this study, participants with depression will be offered antidepressant medication at no cost. During the study, the investigators use brain scans to learn more about brain chemistry in health and depression.
Detailed description
The study involves four overnight stays, three occurring consecutively and one occurring at a separate timepoint. For the three-night consecutive stay, on Overnight-1, sleep can occur as normal and the investigators will measure hormone levels during sleep. On Overnight-2, participants will be kept awake for around 36 hours. On Overnight-3, the investigators will measure hormone levels again during sleep. During a separately scheduled single overnight session (which happens sometime before or after the three-night consecutive stay), three sets of imaging over the course of the night are performed. The imaging is positron emission tomography (PET). It is designed to look at brain chemistry (particularly glutamate receptors in the brain). Participants may sleep in between scans. All participants with depression enrolled in the study will be seen by a clinician throughout the study and offered medication at no cost after the study.
Aim 1: Assess circadian (sleep/wake) phase in depressed and non-depressed individuals. Melatonin secretion is now an easily accessible circadian marker. Further, the average time interval between dim light melatonin onset (DLMO, the time at which melatonin rises above a certain threshold, "the most accurate biomarker of circadian phase position") and sleep midpoint (average bedtime plus half the average sleep duration) has been established as 6 hours in non-depressed participants and likely deviates from this optimum in major depressive disorder (MDD). For this reason, the investigators will measure melatonin in the blood on overnight visit 1.
Hypothesis 1. Average phase angle difference (DLMO - sleep midpoint) will be 6 hours (optimal) in healthy controls, but not depressed, participants.
Hypothesis 2. MDD severity (assessed by the Hamilton Depression Rating Scale, HDRS) will be correlated with deviation from optimal phase angle difference.
Aim 2: Assess brain chemistry (specifically one of the glutamate receptors, the metabotropic glutamate receptor subtype 5, mGluR5) expression at 3 times: the time of DLMO, peak and nadir of melatonin secretion (as measured from overnight visit 1). mGluR5 availability will be assessed near these times to capture mGluR5 circadian rhythmicity using PET and a tracer specific for mGluR5, [11C]ABP688.
Hypothesis 3. mGluR5 variation will be inverse to that of melatonin in both cohorts.
Aim 3: Determine the effect of acute sleep deprivation on circadian rhythms. Within approximately one week of Aims 1 \& 2, all participants will receive sleep deprivation therapy. Following up to 36 hours of wakefulness (shown to increase mGluR5 at a single time point), the investigators will measure acute effects with repeat assessments of melatonin and depression severity. This will thus require two overnight stays in a row- one for the sleep deprivation and then the next to measure melatonin again in the blood while the participant sleeps.
Hypothesis 4. Sleep deprivation will be most successful in the depressed participants with greatest disruption in phase (Aim 1).
Hypothesis 5: Depressed participants will experience greater changes in phase angle difference following sleep deprivation than non-depressed participants.
Aim 4: To determine whether reliable estimates of [11C]ABP688 in plasma can be obtained using a miniPET scanner. [11C]ABP688 concentration will be measured at the wrist or leg with a novel synchronized PET scanner developed by Stony Brook Investigator, Dr. Paul Vaska. This innovative device provides estimates of plasma radioactivity simply by placing the participant's wrist or leg in a mini-PET scanner called versaPET. The radioactivity derived from this wrist or leg scanner, as well as the resulting outcome measures, will be compared to those estimated using blood analysis. This could make future PET studies easier by finding a substitute for blood sampling during the PET scan.
Uncovering the link between mGluR5, circadian disruption and MDD could:
(1) Identify biological underpinnings of circadian (sleep/wake) dysfunction; (2) Identify individuals (those with mGluR5 disruption) for whom treatments like sleep deprivation would be most effective; and (3) Increase use of this safe and rapid treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Other: Sleep Deprivation |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (16 listed)
- Participant considered at significant risk for suicide
- Unlikely to tolerate medication washout or the drug free period following washout (depressed participants only)
- Current psychosis
- ECT within 4 weeks of the first overnight visit
- Significant active physical illness or neurological deficit that may affect brain function or imaging
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 |
|---|---|---|
| Sleep DeprivationOn the first night, the participant sleeps normally as we assess their melatonin through blood work. On the second night, the participant has 3 PET/MRI scans. On the third night, the participant undergoes sleep deprivation. On the fourth night, the participant sleeps normally and we assess their melatonin again through blood work. Depression scores are taken before and after the intervention. | Other | Intervention |
Primary outcome
Measure circadian phase in depressed and non-depressed individuals using the following outcome measure: phase angle difference (DLMO - sleep midpoint, units: hours)
Time frame: 8 Weeks
Hypothesis 1. Average phase angle difference (DLMO - sleep midpoint) will be 6 hours (optimal) in non-depressed participants. Hypothesis 2. MDD severity (assessed by the Hamilton Depression Rating Scale, HDRS) will be correlated with deviation from optimal phase angle difference. For this hypothesis, two outcome measures (phase angle difference, in hours) and HDRS (unitless, ranges from 0 to 52, higher numbers indicate worse depression severity) will be combined in the following way: the Pearson correlation coefficient will be assessed between the phase angle difference and HDRS of each individual. The correlation coefficient will be reported, and is expected to be positive.
3 secondary outcomes
Measure mGluR5 expression (outcome measure: volume of distribution divided by free fraction) at the time of DLMO, peak and nadir of melatonin secretion.
Time frame: 8 Weeks
Measure the effect of acute sleep deprivation on circadian rhythms (outcome measure: shift of the concentration of melatonin over time curve).
Time frame: 8 Weeks
To determine whether reliable estimates of [11C]ABP688 in plasma can be obtained using a miniPET scanner.
Time frame: 8 Weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2025.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sleep Deprivation in people with Depression; Major Depressive Disorder, 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 0 inclusion and 16 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: finished, as of the sponsor's last update on 17 Jul 2025. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure circadian phase in depressed and non-depressed individuals using the following outcome measure: phase angle difference (DLMO - sleep midpoint, units: hours) (time frame: 8 Weeks). 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 Jul 2025.