Major Depressive DisorderNCT05893173
Pilot Study: Establishing Glutamatergic Changes in Rapid Antidepressant Effects of Sleep Deprivation
An observational study of Major Depressive Disorder, run by University of Pennsylvania at 1 site in United States.
Trial summary
In the treatment of Major Depressive Disorder (MDD), total sleep deprivation can produce rapid but short-lasting improvements in mood. In order to develop a new generation of treatments with rapid and sustained efficacy, a better understanding of the mechanism of action is urgently needed. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Sleep Deprivation
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jun 2023to 2 Feb 2025
- Phase
- Observational
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: This pilot study is targeting N=10 subjects (10 depressed patients). We will recruit outpatients with current depression from the Philadelphia and University of Pennsylvania community.
Who may be able to join
- Age between 18 and 85 years; Current depression as assessed on the SCID;
- Stable, normally-timed sleep-wake cycle as determined by interview, 1 week daily sleep log, and defined by:
- Habitual nocturnal sleep duration between 6h and 9h.
- Habitual morning awakening between 0600h and 0800h. Able to comprehend English, as all questionnaires are in this language Ability to provide informed consent
Who cannot join
- Shift work, transmeridian travel or irregular sleep/wake routine in past 60 days; A sleep disorder other than insomnia, as determined by history or actigraph; History of bipolar disorder, delirium, dementia, amnestic disorder, schizophrenia and other psychotic disorders as assessed on the SCID; Previous electroconvulsive therapy in the past 6 months; Alcohol or drug abuse in the past year based upon the SCID or urine toxicology screen; A current smoker; Any significant medical or neurological illness that impacts brain function or impedes participation; History of head trauma with significant loss of consciousness; Metallic implants, pacemakers or tattoos, or other contraindications to MRI; Claustrophobic, or intolerant of the scanner environment; Visual or auditory impairment severe enough to compromise task performance as judged by the PI; For women, pregnancy will exclude participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Pilot Study: Establishing Glutamatergic Changes as the Mechanism of Action in the Rapid Antidepressant Effects of Sleep Deprivation
In the treatment of Major Depressive Disorder (MDD), total sleep deprivation can produce rapid but short-lasting improvements in mood. In order to develop a new generation of treatments with rapid and sustained efficacy, a better understanding of the mechanism of action is urgently needed. One candidate mechanism is the modulation of synaptic strength mediated by glutamatergic activity as sleep deprivation has been suggested to increase synaptic strength. Although determining how sleep deprivation impacts the glutamatergic system is essential to isolating its mechanism of action, the invasive nature of most assessment methods has limited our ability to do so in humans. The proposed research aims to determine if changes in glutamatergic activity, reflecting the modulation of synaptic strength, underlie the antidepressant effects of sleep deprivation. In this project, the investigators will utilize a novel measure of glutamate imaging, GluCEST, to assess changes in glutamatergic activity, in addition to using a proxy measure, waking EEG theta activity, to assess synaptic strength following total sleep deprivation. Ten individuals (aged 18-85) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging and waking EEG prior to and following approximately 30 hours of total sleep deprivation. Both clinician-administered and subjective mood measures will be collected. It is predicted that sleep deprivation will improve mood and increase glutamatergic activity and synaptic strength. Results from this project have the potential to identify the modifiable mechanisms by which rapid antidepressants work which could ultimately stimulate the development of novel interventions that work through the modulation of glutamatergic activity.
Read the detailed description
Consent and Virtual Screening Participants who meet initial inclusion criteria via phone screen will be invited to the complete a virtual visit that will include additional screening (e.g. Medical history), Structured Clinical Interview for DSMV (SCID) and clinician-administered measures of mood to determine final study eligibility. This visit will be conducted virtually to limit the number of in-person study visits. At the outset of this visit, all participants will receive verbal and written explanation of the general goals and risks of the study and will virtually sign an informed consent.
The results of the SCID will be used to characterize the study population and to determine whether they meet criteria for any diagnoses that would preclude participation (e.g. psychotic disorders). Their medical history will be reviewed by a study staff member to ensure that patients are diagnostically eligible.
At-home Sleep Recording For 7 days prior to the in-lab study visit, participants will be asked to keep an at-home sleep schedule, consistent with their habitual sleep/wake schedule (e.g., 10:30 PM 6:00 AM). Participants will also consent to refraining from napping, using alcohol and drugs, and limiting caffeine use to one caffeinated beverage before noon on the day of study. These procedures will be confirmed using sleep diary. Sleep diaries will be completed via the REDCap web-based application if participants feel comfortable with an internet-based platform and have consistent Internet access. Paper and pencil versions of sleep diaries will also be available. Study staff will compare across these methods to verify adherence to study guidelines prior to the in-lab study.
In-laboratory Study Protocol Throughout in-laboratory period, participants will be continuously behaviorally monitored by trained staff in a semi-isolated living area, and have contact with only nurses and research. No caffeinated products will be allowed. When not being tested during the study, participants will be permitted to watch television, converse with the study monitors or play games. Physical activity will be kept to a minimum to avoid any effect of exercise on circadian rhythms or sleep. They will not be allowed to leave the study venue.
Day 1 (D1) Participants will arrive at the Clinical Research Center for Sleep (CRCS) in the afternoon of their scheduled overnight, at no later than 1700h. Following their arrival and orientation, participants are accompanied to the MRI for the neuroimaging protocol to acquire data on rested baseline brain activity before sleep deprivation. Following the neuroimaging protocol, participants will return to CRCS and complete mood assessments (HAM-D, PANAS, VAS, POMS).
Night 1 (N1; Sleep deprivation). Sleep will not be permitted from the end of D1 until 1400h on D2 (approximately 30 hours).
Day 2 (D2) Following breakfast at approximately 0700h, all participants will again complete mood assessments. Participants will complete the neuroimaging protocol again between 0900-1200h. Following the neuroimaging protocol, participants will be discharged or allowed to remain in the CRCS for recovery sleep.
- Conditions
- Major Depressive Disorder
- Being tested
- Sleep Deprivation
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sleep DeprivationBehavioural
Ten individuals (aged 18-85) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging prior to and following approximately 30 hours of total sleep deprivation.
| Study group | Role | What they receive |
|---|---|---|
| Major Depressive Disorder | Ten individuals (aged 18-85) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging and waking EEG prior to and following approximately 30 hours of total sleep deprivation. Receives: Behavioral: Sleep Deprivation |
What is being measured
The primary outcome is the main question the study is designed to answer.
GluCEST imaging metrics
relative change in glutamate concentration (% baseline)
Measured: after 24 hours of sleep deprivation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2023
- Study start19 Jun 2023
- Primary completion2 Feb 2025
- Study completion2 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05893173
- Sponsor's protocol ID
- 853162
- Status last verified
- Feb 2025
- First submitted
- 12 May 2023
- Last updated
- 27 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study: Establishing Glutamatergic Changes as the Mechanism of Action in the Rapid Antidepressant Effects of Sleep Deprivation
- ClinicalTrials.gov ID
- NCT05893173
- Acronym / sponsor ID
- 853162
- Conditions
- Major Depressive Disorder
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 19 Jun 2023 (actual)
- Primary completion
- 2 Feb 2025 (actual)
- Study completion
- 2 Feb 2025 (actual)
- First posted
- 7 Jun 2023 (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.
In the treatment of Major Depressive Disorder (MDD), total sleep deprivation can produce rapid but short-lasting improvements in mood. In order to develop a new generation of treatments with rapid and sustained efficacy, a better understanding of the mechanism of action is urgently needed. One candidate mechanism is the modulation of synaptic strength mediated by glutamatergic activity as sleep deprivation has been suggested to increase synaptic strength. Although determining how sleep deprivation impacts the glutamatergic system is essential to isolating its mechanism of action, the invasive nature of most assessment methods has limited our ability to do so in humans. The proposed research aims to determine if changes in glutamatergic activity, reflecting the modulation of synaptic strength, underlie the antidepressant effects of sleep deprivation. In this project, the investigators will utilize a novel measure of glutamate imaging, GluCEST, to assess changes in glutamatergic activity, in addition to using a proxy measure, waking EEG theta activity, to assess synaptic strength following total sleep deprivation. Ten individuals (aged 18-85) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging and waking EEG prior to and following approximately 30 hours of total sleep deprivation. Both clinician-administered and subjective mood measures will be collected. It is predicted that sleep deprivation will improve mood and increase glutamatergic activity and synaptic strength. Results from this project have the potential to identify the modifiable mechanisms by which rapid antidepressants work which could ultimately stimulate the development of novel interventions that work through the modulation of glutamatergic activity.
Detailed description
Consent and Virtual Screening Participants who meet initial inclusion criteria via phone screen will be invited to the complete a virtual visit that will include additional screening (e.g. Medical history), Structured Clinical Interview for DSMV (SCID) and clinician-administered measures of mood to determine final study eligibility. This visit will be conducted virtually to limit the number of in-person study visits. At the outset of this visit, all participants will receive verbal and written explanation of the general goals and risks of the study and will virtually sign an informed consent.
The results of the SCID will be used to characterize the study population and to determine whether they meet criteria for any diagnoses that would preclude participation (e.g. psychotic disorders). Their medical history will be reviewed by a study staff member to ensure that patients are diagnostically eligible.
At-home Sleep Recording For 7 days prior to the in-lab study visit, participants will be asked to keep an at-home sleep schedule, consistent with their habitual sleep/wake schedule (e.g., 10:30 PM 6:00 AM). Participants will also consent to refraining from napping, using alcohol and drugs, and limiting caffeine use to one caffeinated beverage before noon on the day of study. These procedures will be confirmed using sleep diary. Sleep diaries will be completed via the REDCap web-based application if participants feel comfortable with an internet-based platform and have consistent Internet access. Paper and pencil versions of sleep diaries will also be available. Study staff will compare across these methods to verify adherence to study guidelines prior to the in-lab study.
In-laboratory Study Protocol Throughout in-laboratory period, participants will be continuously behaviorally monitored by trained staff in a semi-isolated living area, and have contact with only nurses and research. No caffeinated products will be allowed. When not being tested during the study, participants will be permitted to watch television, converse with the study monitors or play games. Physical activity will be kept to a minimum to avoid any effect of exercise on circadian rhythms or sleep. They will not be allowed to leave the study venue.
Day 1 (D1) Participants will arrive at the Clinical Research Center for Sleep (CRCS) in the afternoon of their scheduled overnight, at no later than 1700h. Following their arrival and orientation, participants are accompanied to the MRI for the neuroimaging protocol to acquire data on rested baseline brain activity before sleep deprivation. Following the neuroimaging protocol, participants will return to CRCS and complete mood assessments (HAM-D, PANAS, VAS, POMS).
Night 1 (N1; Sleep deprivation). Sleep will not be permitted from the end of D1 until 1400h on D2 (approximately 30 hours).
Day 2 (D2) Following breakfast at approximately 0700h, all participants will again complete mood assessments. Participants will complete the neuroimaging protocol again between 0900-1200h. Following the neuroimaging protocol, participants will be discharged or allowed to remain in the CRCS for recovery sleep.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Major Depressive Disorder | – | Behavioral: Sleep DeprivationTen individuals (aged 18-85) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging and waking EEG prior to and following approximately 30 hours of total sleep deprivation. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- This pilot study is targeting N=10 subjects (10 depressed patients). We will recruit outpatients with current depression from the Philadelphia and University of Pennsylvania community.
Key inclusion criteria (4 listed)
- Age between 18 and 85 years; Current depression as assessed on the SCID;
- Stable, normally-timed sleep-wake cycle as determined by interview, 1 week daily sleep log, and defined by:
- Habitual nocturnal sleep duration between 6h and 9h.
- Habitual morning awakening between 0600h and 0800h. Able to comprehend English, as all questionnaires are in this language Ability to provide informed consent
Key exclusion criteria (1 listed)
- Shift work, transmeridian travel or irregular sleep/wake routine in past 60 days; A sleep disorder other than insomnia, as determined by history or actigraph; History of bipolar disorder, delirium, dementia, amnestic disorder, schizophrenia and other psychotic disorders as assessed on the SCID; Previous electroconvulsive therapy in the past 6 months; Alcohol or drug abuse in the past year based upon the SCID or urine toxicology screen; A current smoker; Any significant medical or neurological illness that impacts brain function or impedes participation; History of head trauma with significant loss of consciousness; Metallic implants, pacemakers or tattoos, or other contraindications to MRI; Claustrophobic, or intolerant of the scanner environment; Visual or auditory impairment severe enough to compromise task performance as judged by the PI; For women, pregnancy will exclude participation.
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 DeprivationTen individuals (aged 18-85) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging prior to and following approximately 30 hours of total sleep deprivation. | Behavioural | Major Depressive Disorder |
Primary outcome
GluCEST imaging metrics
Time frame: after 24 hours of sleep deprivation
relative change in glutamate concentration (% baseline)
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 27 Feb 2025.
- Individual participant dataSharing planned: No
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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?
An observational study of Major Depressive Disorder, run by University of Pennsylvania 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 4 inclusion and 1 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 27 Feb 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?
GluCEST imaging metrics (time frame: after 24 hours of sleep deprivation). 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 27 Feb 2025.