The OBSERVE Protocol

Recruiting

• Conditions: Major Depression Disorder
• Interventions: Drug: Spravato; Drug: IV Ketamine

• Registration Number: NCT06725277
• Lead Sponsor: Yale University

Brief 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.

This 5-year, 6-site study will enroll 450 total patients. The sites will comprise 3 academic medical centers and 3 community psychiatric practices.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-01-21
• Study First Submitted: 2024-12-05
• Study First Submitted QC: 2024-12-05
• Study First Posted: 2024-12-10
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-02
• Last Update Posted: 2025-05-06
• Primary Completion: 2029-12
• Study Completion: 2029-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet the following criteria:

1. 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

2. 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:

3. Adult ages 18 or older

4. Provision of signed and dated informed consent form prior to any study procedures

5. Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Diagnosis of bipolar disorder or psychotic disorder (i.e., schizophrenia, schizoaffective disorder)
2. Other psychiatric comorbidities are permitted so long as depression is the predominant diagnosis
3. Active or recent (within 12 months) substance use disorder (other than nicotine)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Spravato	Spravato	Patients taking Spravato, an intranasal form of ketamine
IV Ketamine	IV Ketamine	Patients taking IV ketamine

Primary Outcome Measures

Name	Time	Method
TSQM-9	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.

Secondary Outcome Measures

Name	Time	Method
Depression Severity (Self Report)	baseline to 6 months	Change in 16-Item Quick Inventory of Depressive Symptomatology (QIDS). Score ranges from 0 - 27, with higher scores indicating worse depression.
Depression Severity (Clinician Report)	baseline to 6 months	Change in Montgomery-Åsberg Depression Rating Scale (MADRS). Scores range from 0 - 60, with higher scores indicating worse depression.
Measure of Treatment Patterns: Number of treatments	baseline to 6 months	Total number of treatments (ketamine or esketamine) during the study
Measure of Treatment Patterns: Reasons for Discontinuation	baseline to 6 months	Number and proportion of patients who discontinue treatment
Measure of Treatment Patterns: Average Dose	baseline to 6 months	Descriptive measures of average dose of ketamine / esketamine
Measures of Adverse Events	Baseline to 6 months	Total number of serious adverse events possibly related to IV ketamine or esketamine

Trial Locations

Locations (6)

Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Mood Institute; 🇺🇸 Milford, Connecticut, United States

Yale School of Medicine; 🇺🇸 New Haven, Connecticut, United States

LifeStance Health; 🇺🇸 Moore, Oklahoma, United States

Houston Center for Advanced Psychiatric Treatment; 🇺🇸 Bellaire, Texas, United States