Ketamine for the Treatment of Opioid Use Disorder and Depression

• ClinicalTrials.gov Identifier: NCT04177706
• Recruitment Status: Recruiting
• First Posted: November 26, 2019
• Last Update Posted: January 11, 2021
• Sponsor: Medical University of South Carolina
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Jennifer Jones, Medical University of South Carolina

Tracking Information

• First Submitted Date: November 22, 2019
• First Posted Date: November 26, 2019
• Last Update Posted Date: January 11, 2021
• Actual Study Start Date: December 17, 2020
• Estimated Primary Completion Date: December 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 22, 2019)

• Percentage of Individuals Completing Informed Consent [ Time Frame: Outcomes will be cumulatively assessed from the time that the first participant is screened through the time that the last participant is enrolled. Estimated time frame of: 23 months. ]
  Primary outcomes will be 1) the percentage of individuals completing informed consent out of the number of individuals eligible on the initial screening.
• Percentage of Individuals Completing the Full Protocol [ Time Frame: Outcomes will be cumulatively assessed from the time that the first participant completes informed consent through the time that the last participant completes the final follow-up visit. Estimated time frame of: 23 months. ]
  The other primary outcome will be the percentage of individuals that complete informed consent which complete the full protocol.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 22, 2019)

Change in Depression Severity [ Time Frame: Baseline through 4 week follow-up. ]

Secondary outcomes will include changes in depression severity (as measured on the Montgomery-Asberg Depression Rating Scale), which will be calculated as a change from baseline to 4-week followup. Montgomery Asberg Depression Rating Scale (MADRS; Montgomery, 1979). The MADRS is a clinician administered, 10-item questionnaire of depression severity. The total score ranges from 0-60, with scores of 0-6 considered normal (non-depressed), 7-19 indicative of mild depression, 20-34 indicative of moderate depression, and 35-60 indicative of severe depression. Individuals scoring 20 or higher on the MADRS will be included in the study. The MADRS evaluates the following symptoms of depression: 1) clinical appearance of sadness, 2) self-reported sadness, 3) inner tension, 4) reduced sleep, 5) reduced appetite, 6) concentration difficulties, 7) lassitude, 8) inability to feel, 9) pessimistic thought process, and 10) thoughts of suicide.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ketamine for the Treatment of Opioid Use Disorder and Depression
• Official Title: A Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Efficacy of Ketamine for the Treatment of Concurrent Opioid Use Disorder and Major Depressive Disorder
• Brief Summary: The purpose of the study is to examine whether an investigational medication called ketamine is able to improve treatment outcomes for concurrent opioid addiction and depression when used in conjunction with buprenorphine treatment. Study medications will be delivered twice per week for four weeks. If you are eligible and you decide to enroll in the study, your participation will last approximately 8 weeks, or 2 months.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Depression
• Opioid-use Disorder
• Opioid Abuse

Intervention

• Drug: Ketamine Hydrochloride
  Participants receiving the active study medication will receive 60 mg ketamine twice per week for four weeks under clinical supervision.
• Drug: Placebo
  Participants receiving the placebo study medication will receive saline twice per week for four weeks under clinical supervision.

Study Arms

• Experimental: Group A (Ketamine)
  Intervention: Drug: Ketamine Hydrochloride
• Placebo Comparator: Group B (Placebo)
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 22, 2019): 30
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 1, 2021
• Estimated Primary Completion Date: December 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Between the ages of 18 to 65 years old.
2. Able to provide informed consent.
3. Meet DSM-5 criteria for Major Depressive Disorder, without psychotic features.
4. Score at least 20 on the Montgomery-Asberg Depression Rating Scale.
5. Fulfill a minimum of 4 of 11 current opioid use disorder criteria by DSM-5.
6. Have used opioids illicitly at least once in the past month.
7. Subjects must be on standard of care pharmacotherapy for OUD (buprenorphine) for at least one month.
8. Subjects taking other psychotropic medications (e.g. anti-depressants or non benzodiazepine anxiolytics) must be maintained on a stable dose for at least four weeks before study initiation.
9. Subjects must be considered to have treatment-refractory MDD as evidenced by failure or only partial response to treatment with at least two standard of care pharmacotherapy antidepressants.
10. Must consent to random assignment to intranasal ketamine or placebo control.

Exclusion Criteria:

They are considered an immediate suicide risk (by Columbia Suicide Severity Rating Scale of 4 or greater, a history of a suicide attempt in the past year, or by clinician judgment) or felt to be likely to require hospitalization during the course of the study.

2. They have a self-reported history of illicit ketamine use, or baseline urine drug testing positive for ketamine.

3. They are in acute opioid withdrawal (as evidenced by a score of 5 or above on the Clinician Opioid Withdrawal Scale). These subjects will be referred for clinical detoxification and pharmacotherapy induction. Subjects may be re-assessed for study eligibility after one month of treatment with a standard of care OUD pharmacotherapy.

4. Subjects who meet DSM-5 criteria for current bipolar disorder. 5. Subjects who meet DSM-5 criteria for current or history of psychotic spectrum disorders.

6. Women who are pregnant or nursing. 7. Subjects with current hypertension as defined by a systolic blood pressure (SBP) >140 mmHg or a diastolic blood pressure (DBP) >90 mmHg.

8. Subjects with a self-reported history of delirium for any cause. 9. A history of allergic or other adverse reaction to ketamine. 10. Clinically significant abnormal laboratory values, physical exam findings or self-reported medical conditions for which a transient increase in blood pressure could be significantly detrimental (e.g. glaucoma, brain aneurysms, cardiovascular disease, or end-stage renal disease).

11. Electrocardiogram (ECG) findings (obtained within thirty days prior to randomization) of tachycardia, prior myocardial infarction, myocardial ischemia, or aberrant conduction).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Melissa Michel; 843-792-1901; michelm@musc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04177706
• Other Study ID Numbers: 00091292; K12DA031794 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Jennifer Jones, Medical University of South Carolina
• Study Sponsor: Medical University of South Carolina
• Collaborators: National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Jennifer Jones, MD; Medical University of South Carolina

• PRS Account: Medical University of South Carolina
• Verification Date: January 2021