Depression, Opioid Abuse, Opioid-use Disorder
Conditions
Keywords
Ketamine
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.
Interventions
DRUGKetamine Hydrochloride
Participants receiving the active study medication will receive 60 mg ketamine twice per week for four weeks under clinical supervision.
DRUGPlacebo
Participants receiving the placebo study medication will receive saline twice per week for four weeks under clinical supervision.
Sponsors
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Individuals Completing Informed Consent | Actual 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 | Actual time frame 23 months. | The other primary outcome will be the percentage of individuals that complete informed consent which complete the full interventional protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Depression Severity | Baseline through 4-week interventional visits (8th interventional visit). | 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 weeks (8th interventional visit). 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A (Ketamine) Ketamine Hydrochloride: Participants receiving the active study medication will receive 60 mg ketamine twice per week for four weeks under clinical supervision. | 11 |
| Group B (Placebo) Placebo: Participants receiving the placebo study medication will receive saline twice per week for four weeks under clinical supervision. | 10 |
| Total | 21 |
Baseline characteristics
| Characteristic | Group B (Placebo) | Total | Group A (Ketamine) |
|---|---|---|---|
| Age, Continuous | 37 years | 36 years | 35 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 9 Participants | 18 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 10 |
| other Total, other adverse events | 0 / 11 | 0 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 |
Outcome results
Primary
Percentage of Individuals Completing Informed Consent
Primary outcomes will be 1) the percentage of individuals completing informed consent out of the number of individuals eligible on the initial screening.
Time frame: Actual time frame of: 23 months.
Population: Outcomes will be cumulatively assessed from the time that the first participant is screened through the time that the last participant completes informed consent. There is only a single cohort (single arm/group) until randomization, which happens at the first interventional visit. Actual time frame of: 23 months.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Percentage of Individuals Completing Informed Consent | Percentage of Individuals Completing Informed Consent | 34 Participants |
Primary
Percentage of Individuals Completing the Full Protocol
The other primary outcome will be the percentage of individuals that complete informed consent which complete the full interventional protocol.
Time frame: Actual time frame 23 months.
Population: There is only a single cohort (single arm/group) until randomization, which happens at the first interventional visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Percentage of Individuals Completing Informed Consent | Percentage of Individuals Completing the Full Protocol | 11 Participants |
Secondary
Change in Depression Severity
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 weeks (8th interventional visit). 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.
Time frame: Baseline through 4-week interventional visits (8th interventional visit).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Percentage of Individuals Completing Informed Consent | Change in Depression Severity | 30 score on a scale | Standard Deviation 2.8 |
| Group B (Placebo) | Change in Depression Severity | 10.8 score on a scale | Standard Deviation 14.1 |