Major Depression DisorderNCT06725277
The OBSERVE Protocol
An observational study of Major Depression Disorder, run by Yale University at 8 sites in United States.
Trial summary
This observational protocol is intended to provide long-term follow-up data on patients initiating or continuing treatment with either Spravato® or IV ketamine. This can provide us information on the patient acceptability and satisfaction, patterns of use, long-term effectiveness, and safety of the two approaches. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Major Depression Disorder
- What is being tested?
- Spravato and IV Ketamine
- Type of treatment
- Injection or infusion
- How many people
- 450 participants
- Where
- 8 sitesUnited States
- Study dates
- 21 Jan 2024to Dec 2029
- How long will I take part?
- 60 Months
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Study population includes adults ages 18 or older with a diagnosis of major depressive disorder that is refractory to two or more antidepressant trials that have moderate to severe depression based on an initial MADRS score of 25 or greater having recently initiated treatment with appropriate baseline measures obtained (treatment-continuing) or scheduled to initiate standard clinical care (treatment-initiating) with either IV ketamine or Spravato® treatment.
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet the following criteria:
- Recently started treatment (within 75 days of screening visit) with IV ketamine or Spravato® as prescribed by a clinician for the treatment of moderate to severe (based on an initial MADRS score ≥ 25) TRD (refractory to two or more antidepressant trials) without psychotic features and having appropriate baseline measures collected before starting treatment. These patients are referred to as treatment-continuing subjects.
- OR
- Scheduled to receive standard clinical treatment with IV ketamine or Spravato® as prescribed by a clinician for the treatment of moderate to severe (based on an initial MADRS score ≥ 25) TRD (refractory to two or more antidepressant trials) without psychotic features. These patients are referred to as treatment-initiating subjects.
- In addition, in order to be eligible, an individual must meet all of the following additional criteria:
- Adult ages 18 or older
- Provision of signed and dated informed consent form prior to any study procedures
- Stated willingness to comply with all study procedures and availability for the duration of the study
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Diagnosis of bipolar disorder or psychotic disorder (i.e., schizophrenia, schizoaffective disorder)
- Other psychiatric comorbidities are permitted so long as depression is the predominant diagnosis
- Active or recent (within 12 months) substance use disorder (other than nicotine)
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
United States8 sites, 6 recruiting
- Active, not recruiting
University of Michigan
Ann Arbor, Michigan, 48104
- Recruiting
Emory University
Atlanta, Georgia, 30322
Brandon Kitay, MD, PhD, 404-712-6939
- Recruiting
Houston Center for Advanced Psychiatric Treatment
Bellaire, Texas, 77401
Sandhya Prashad, MD
Sarah Hartigan, (832) 730 - 5196, sarah@sprashadmd.com
- Recruiting
Mood Institute
Milford, Connecticut, 06461
Lisa Harding, MD, 203-701-9737, Trials@DepressionMD.com
Lisa Harding, MD
- Active, not recruiting
LifeStance Health
Moore, Oklahoma, 73160
- Recruiting
Athena Care
Nashville, Tennessee, 37228
Amanda Sparks-Bushnell, MD, 615-861-1000, interventional@athenacare.health
Amanda Sparks-Bushnell, MD
- Recruiting
Yale School of Medicine
New Haven, Connecticut, 06512
- Recruiting
Seattle NTC
Seattle, Washington, 98104
Rebecca Allen, MD, 206-467-6300 ext. 5, Rebecca.Allen@seattlentc.com
Rebecca Allen, MD
About this study
Official title: Comparative Effectiveness of Racemic Ketamine Versus Esketamine (Spravato®) for Depression: The OBSERVE Protocol
This observational protocol is intended to provide long-term follow-up data on patients initiating or continuing treatment with either Spravato® or IV ketamine. This can provide us information on the patient acceptability and satisfaction, patterns of use, long-term effectiveness, and safety of the two approaches.
This 5-year, 6-site study will enroll 450 total patients. The sites will comprise 3 academic medical centers and 3 community psychiatric practices.
- Conditions
- Major Depression Disorder
- Being tested
- Spravato, IV Ketamine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SpravatoDrug
Intranasal esketamine
IV KetamineDrug
IV ketamine
| Study group | Role | What they receive |
|---|---|---|
| IV Ketamine | Patients taking IV ketamine Receives: Drug: IV Ketamine | |
| Spravato | Patients taking Spravato, an intranasal form of ketamine Receives: Drug: Spravato |
What is being measured
The primary outcome is the main question the study is designed to answer.
TSQM-9
9-Item Treatment Satisfaction Questionnaire for Medication (TSQM-9). Analyses will be done for the whole sample as well as for treatment-continuing patients who recently completed a randomized trial of ketamine v. esketamine (EQUIVALENCE). The primary analysis for this measure will analyze treatment-continuing patients. Scores range from 0 - 100 with higher scores indicating higher satisfaction.
Measured: baseline to 6 months
Secondary outcomes (6)
Depression Severity (Self Report)
Change in 16-Item Quick Inventory of Depressive Symptomatology (QIDS). Score ranges from 0 - 27, with higher scores indicating worse depression.
Measured: baseline to 6 months
Depression Severity (Clinician Report)
Change in Montgomery-Åsberg Depression Rating Scale (MADRS). Scores range from 0 - 60, with higher scores indicating worse depression.
Measured: baseline to 6 months
Measure of Treatment Patterns: Number of treatments
Total number of treatments (ketamine or esketamine) during the study
Measured: baseline to 6 months
Measure of Treatment Patterns: Reasons for Discontinuation
Number and proportion of patients who discontinue treatment
Measured: baseline to 6 months
Measure of Treatment Patterns: Average Dose
Descriptive measures of average dose of ketamine / esketamine
Measured: baseline to 6 months
Measures of Adverse Events
Total number of serious adverse events possibly related to IV ketamine or esketamine
Measured: Baseline to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2024
- Study start21 Jan 2024
- Primary completionDec 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depression DisorderStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 450 participants (estimated)
- Target duration
- 60 Months
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Responsible party
- Sponsor
- Investigators
- Samuel Wilkinson, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06725277
- Sponsor's protocol ID
- 2000038673
- Other IDs
- 23-005287
- Status last verified
- Sep 2026
- First submitted
- 5 Dec 2024
- Last updated
- 3 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 3 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparative Effectiveness of Racemic Ketamine Versus Esketamine (Spravato®) for Depression: The OBSERVE Protocol
- ClinicalTrials.gov ID
- NCT06725277
- Acronym / sponsor ID
- 2000038673
- Conditions
- Major Depression Disorder
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Study start
- 21 Jan 2024 (actual)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 10 Dec 2024 (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 observational protocol is intended to provide long-term follow-up data on patients initiating or continuing treatment with either Spravato® or IV ketamine. This can provide us information on the patient acceptability and satisfaction, patterns of use, long-term effectiveness, and safety of the two approaches.
This 5-year, 6-site study will enroll 450 total patients. The sites will comprise 3 academic medical centers and 3 community psychiatric practices.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 60 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IV Ketamine | – | Drug: IV KetaminePatients taking IV ketamine |
| Spravato | – | Drug: SpravatoPatients taking Spravato, an intranasal form of ketamine |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Study population includes adults ages 18 or older with a diagnosis of major depressive disorder that is refractory to two or more antidepressant trials that have moderate to severe depression based on an initial MADRS score of 25 or greater having recently initiated treatment with appropriate baseline measures obtained (treatment-continuing) or scheduled to initiate standard clinical care (treatment-initiating) with either IV ketamine or Spravato® treatment.
Key inclusion criteria (8 listed)
- In order to be eligible to participate in this study, an individual must meet the following criteria:
- Recently started treatment (within 75 days of screening visit) with IV ketamine or Spravato® as prescribed by a clinician for the treatment of moderate to severe (based on an initial MADRS score ≥ 25) TRD (refractory to two or more antidepressant trials) without psychotic features and having appropriate baseline measures collected before starting treatment. These patients are referred to as treatment-continuing subjects.
- OR
- Scheduled to receive standard clinical treatment with IV ketamine or Spravato® as prescribed by a clinician for the treatment of moderate to severe (based on an initial MADRS score ≥ 25) TRD (refractory to two or more antidepressant trials) without psychotic features. These patients are referred to as treatment-initiating subjects.
- In addition, in order to be eligible, an individual must meet all of the following additional criteria:
Key exclusion criteria (4 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Diagnosis of bipolar disorder or psychotic disorder (i.e., schizophrenia, schizoaffective disorder)
- Other psychiatric comorbidities are permitted so long as depression is the predominant diagnosis
- Active or recent (within 12 months) substance use disorder (other than nicotine)
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 |
|---|---|---|
| SpravatoIntranasal esketamine | Drug | Spravato |
| IV KetamineIV ketamine | Drug | IV Ketamine |
Primary outcome
TSQM-9
Time frame: baseline to 6 months
9-Item Treatment Satisfaction Questionnaire for Medication (TSQM-9). Analyses will be done for the whole sample as well as for treatment-continuing patients who recently completed a randomized trial of ketamine v. esketamine (EQUIVALENCE). The primary analysis for this measure will analyze treatment-continuing patients. Scores range from 0 - 100 with higher scores indicating higher satisfaction.
6 secondary outcomes
Depression Severity (Self Report)
Time frame: baseline to 6 months
Depression Severity (Clinician Report)
Time frame: baseline to 6 months
Measure of Treatment Patterns: Number of treatments
Time frame: baseline to 6 months
Measure of Treatment Patterns: Reasons for Discontinuation
Time frame: baseline to 6 months
Measure of Treatment Patterns: Average Dose
Time frame: baseline to 6 months
Measures of Adverse Events
Time frame: Baseline to 6 months
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 3 Sep 2026.
- 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.
Samuel Wilkinson, MD principal investigator
Yale University
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Major Depression Disorder, run by Yale University at 8 sites 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 8 inclusion and 4 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 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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?
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 Cindy Voghell (203-737-4784, cynthia.voghell@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TSQM-9 (time frame: baseline to 6 months). 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 3 Sep 2026.