Opioid Use DisorderPhase 1NCT05051449
Ketamine for OUD and Comorbid Depression (OUDCD)
A Phase 1 study testing Ketamine Hydrochloride in people with Opioid Use Disorder and Depressive Disorder, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
Methadone is a first-line, evidence-based treatment for opioid use disorder (OUD). Unfortunately, retention and adherence in methadone treatment is a major challenge. OUD patients frequently present with co-morbid depression (OUDCD), a risk factor for poor OUD treatment outcomes, overdose, and suicide. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Opioid Use Disorder, Depressive Disorder
- What is being tested?
- Ketamine Hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Apr 2022to 30 Nov 2023
- Phase
- Phase 1
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- From NHS prescreen (no contact, Study Day 0): Between the ages of 18 to 65 years old
- From NHS prescreen (no contact, Study Day 0): Daily use of illicit opioids
- From NHS prescreen (no contact, Study Day 0): Fulfillment of DSM-5/ICD-10 criteria for moderate-to-severe opioid or heroin use disorder
- From NHS prescreen (no contact, Study Day 0): Acceptance into methadone maintenance care for treatment of opioid or heroin use disorder
- From screening for study eligibility (Study Contact Day 1): A total of 10 or more points on the PHQ-9
- From screening for study eligibility (Study Contact Day 1): Have had no prior sustained experience/dependence on ketamine or PCP (i.e., must answer "no" to all four questions on the ketamine/PCP screen)
Who cannot join
- From NHS prescreen (no contact, Study Day 0): Patients transferring from another program of opioid agonist treatment
- From NHS prescreen (no contact, Study Day 0): Electrocardiogram (ECG) findings of tachycardia, prior myocardial infarction, myocardial ischemia, or aberrant conduction
- From NHS prescreen (no contact, Study Day 0): Self-report of recent prescribed or illicit benzodiazepine use ("Xannies", or "bars")
- From NHS prescreen (no contact, Study Day 0): Urine screen positive for pregnancy
- From NHS prescreen (no contact, Study Day 0): Stage 2 hypertension, defined by a systolic blood pressure (SBP) > 140 mmHg or a diastolic blood pressure (DBP) > 90 mmHg
- From NHS prescreen (no contact, Study Day 0): 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., cardiovascular disease), as determined by the evaluating intake physician
Show all 14Show fewer
- From NHS prescreen (no contact, Study Day 0): Any clinically significant abnormal findings from intake health and physical examination
- From NHS prescreen (no contact, Study Day 0): Any indication of serious mental illness or psychiatric disorder from the attending's evaluation notes
- From Liver Function Screen (Study Contact Day 2): Baseline alkaline phosphatase > 2.5 times the upper limit of normal
- From Liver Function Screen (Study Contact Day 2): Baseline aspartate aminotransferase > 3 times the upper limit of normal
- From Psychiatric Evaluation (Study Contact Day 2) Current or previous recreational use of ketamine or PCP
- From Psychiatric Evaluation (Study Contact Day 2): Subjects who meet DSM-5 criteria for current bipolar disorder
- From Psychiatric Evaluation (Study Contact Day 2): Past or current presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder
- Subjects who meet DSM-5 criteria for current or history of psychotic spectrum disorders
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland Baltimore
Baltimore, Maryland, 21223
About this study
Official title: Increasing Retention in Methadone Maintenance Treatment: Feasibility and Preliminary Efficacy of Ketamine for the Treatment of Patients With OUD and Comorbid Depression (OUDCD)
Methadone is a first-line, evidence-based treatment for opioid use disorder (OUD). Unfortunately, retention and adherence in methadone treatment is a major challenge. OUD patients frequently present with co-morbid depression (OUDCD), a risk factor for poor OUD treatment outcomes, overdose, and suicide. The last two decades have seen an exciting and transformational development in the treatment of depression - ketamine. As a safe, rapid-acting anti-depressant deliverable within the context of methadone maintenance treatment, ketamine could feasibly change the landscape of treatment for OUD patients with comorbid depression. This proposal seeks to evaluate implementation outcomes (feasibility and patient acceptance) as well as preliminary efficacy of ketamine on methadone treatment outcomes for OUD patients (n=6) with comorbid depression and depressive symptoms presenting for methadone treatment.
- Conditions
- Opioid Use Disorder, Depressive Disorder
- Being tested
- Ketamine Hydrochloride
- Medical subject headings
- Opioid-Related Disorders, Depressive Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine HydrochlorideDrug
Ketamine will be administered by a nurse in a 2-week treatment phase, during which participants will receive six IV infusions of 0.5 mg/kg (over 40-50 minutes) ketamine three times per week. Infusion days for patients will be on Mondays, Wednesdays, and Fridays, +/- 1 day. Ketamine infusions will take place at the UMB General Clinical Research Center (GCRC). The GCRC nurse will deliver ketamine within a private exam room. The infusions will last 40-50 min, and the participant will be observed by the GCRC clinical staff for 2 hours post-infusion. Vital signs will be monitored throughout the treatment; specifically, blood pressure, pulse ox and heart rate will be checked prior to treatment, q20 minutes during infusion, and q30-60 minutes after infusion for up to three hours.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Not described Receives: Drug: Ketamine Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility: Study Recruitment
Feasibility will be assessed via participant recruitment: 50% of eligible patients approached will consent to participation in the pilot.
Measured: One year
Feasibility: Study Retention
75% of participants will be retained throughout the duration of ketamine infusion procedures
Measured: One year
Patient Acceptability: Acceptability of the Intervention Measure (AIM)
Acceptance will be assessed via scores on the Acceptability of the Intervention Measure (AIM): Distribution summarized with mean and 95% C.I. Scale values range from 1 to 5 with higher mean values representing greater agreement and/or acceptability.
Measured: One month
Patient Acceptability: Engagement
Engagement will be assessed via dosing records of observed ketamine administration: distribution of percentage of completed infusions per patient.
Measured: One month
Secondary outcomes (3)
Patient Treatment Retention
One-month (30-day) methadone treatment retention as a binomial (yes/no) variable outcome.
Measured: Three months
Changes in Psychiatric Diagnosis of Depression
Assessment of changes in depression (MADRS score) will be made at baseline and on the final study day based on a Minimal Clinically Important Difference (MCID) defined change of 1.9 points
Measured: One month
Changes in Depressive Symptoms
Assessment of changes in symptoms of depression, measured with the Patient Health Questionnaire (PHQ-9) will be made at baseline and on the final study day.
Measured: One month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2021
- Study start4 Apr 2022
- Primary completion17 Nov 2023
- Study completion30 Nov 2023
Why it stopped: Study funds were exhausted
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Annabelle Belcher, University of Maryland, Baltimore
- Investigators
- Annabelle Belcher, PhD, Principal investigator, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05051449
- Sponsor's protocol ID
- HP-00096377
- Status last verified
- Mar 2024
- First submitted
- 10 Sep 2021
- Last updated
- 7 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Manza P, Belcher AM, Fitzsimons H, Spaderna M, Greenblatt AD, Smith HC, Derenoncourt M, Gann D, Farooq U, Kvarta MD, DiPaula BA, Merritt S, Mitic I, Zarate CA, Gould TD, Weintraub E, Kattakuzhy SM. Ketamine to enhance methadone treatment retention in patients with opioid use disorder and co-morbid depression. Am J Drug Alcohol Abuse. 2025;51(5):649-657. doi: 10.1080/00952990.2025.2541212. Epub 2025 Aug 22.
PubMed 40844815
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Increasing Retention in Methadone Maintenance Treatment: Feasibility and Preliminary Efficacy of Ketamine for the Treatment of Patients With OUD and Comorbid Depression (OUDCD)
- ClinicalTrials.gov ID
- NCT05051449
- Acronym / sponsor ID
- HP-00096377
- Conditions
- Opioid Use Disorder, Depressive Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study funds were exhausted
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- 4 Apr 2022 (actual)
- Primary completion
- 17 Nov 2023 (actual)
- Study completion
- 30 Nov 2023 (actual)
- First posted
- 21 Sep 2021 (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.
Methadone is a first-line, evidence-based treatment for opioid use disorder (OUD). Unfortunately, retention and adherence in methadone treatment is a major challenge. OUD patients frequently present with co-morbid depression (OUDCD), a risk factor for poor OUD treatment outcomes, overdose, and suicide. The last two decades have seen an exciting and transformational development in the treatment of depression - ketamine. As a safe, rapid-acting anti-depressant deliverable within the context of methadone maintenance treatment, ketamine could feasibly change the landscape of treatment for OUD patients with comorbid depression. This proposal seeks to evaluate implementation outcomes (feasibility and patient acceptance) as well as preliminary efficacy of ketamine on methadone treatment outcomes for OUD patients (n=6) with comorbid depression and depressive symptoms presenting for methadone treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: Ketamine Hydrochloride |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- From NHS prescreen (no contact, Study Day 0): Between the ages of 18 to 65 years old
- From NHS prescreen (no contact, Study Day 0): Daily use of illicit opioids
- From NHS prescreen (no contact, Study Day 0): Fulfillment of DSM-5/ICD-10 criteria for moderate-to-severe opioid or heroin use disorder
- From NHS prescreen (no contact, Study Day 0): Acceptance into methadone maintenance care for treatment of opioid or heroin use disorder
- From screening for study eligibility (Study Contact Day 1): A total of 10 or more points on the PHQ-9
Key exclusion criteria (14 listed)
- From NHS prescreen (no contact, Study Day 0): Patients transferring from another program of opioid agonist treatment
- From NHS prescreen (no contact, Study Day 0): Electrocardiogram (ECG) findings of tachycardia, prior myocardial infarction, myocardial ischemia, or aberrant conduction
- From NHS prescreen (no contact, Study Day 0): Self-report of recent prescribed or illicit benzodiazepine use ("Xannies", or "bars")
- From NHS prescreen (no contact, Study Day 0): Urine screen positive for pregnancy
- From NHS prescreen (no contact, Study Day 0): Stage 2 hypertension, defined by a systolic blood pressure (SBP) > 140 mmHg or a diastolic blood pressure (DBP) > 90 mmHg
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 |
|---|---|---|
| Ketamine HydrochlorideKetamine will be administered by a nurse in a 2-week treatment phase, during which participants will receive six IV infusions of 0.5 mg/kg (over 40-50 minutes) ketamine three times per week. Infusion days for patients will be on Mondays, Wednesdays, and Fridays, +/- 1 day. Ketamine infusions will take place at the UMB General Clinical Research Center (GCRC). The GCRC nurse will deliver ketamine within a private exam room. The infusions will last 40-50 min, and the participant will be observed by the GCRC clinical staff for 2 hours post-infusion. Vital signs will be monitored throughout the treatment; specifically, blood pressure, pulse ox and heart rate will be checked prior to treatment, q20 minutes during infusion, and q30-60 minutes after infusion for up to three hours. | Drug | Ketamine |
Primary outcome
Feasibility: Study Recruitment
Time frame: One year
Feasibility will be assessed via participant recruitment: 50% of eligible patients approached will consent to participation in the pilot.
Feasibility: Study Retention
Time frame: One year
75% of participants will be retained throughout the duration of ketamine infusion procedures
Patient Acceptability: Acceptability of the Intervention Measure (AIM)
Time frame: One month
Acceptance will be assessed via scores on the Acceptability of the Intervention Measure (AIM): Distribution summarized with mean and 95% C.I. Scale values range from 1 to 5 with higher mean values representing greater agreement and/or acceptability.
Patient Acceptability: Engagement
Time frame: One month
Engagement will be assessed via dosing records of observed ketamine administration: distribution of percentage of completed infusions per patient.
3 secondary outcomes
Patient Treatment Retention
Time frame: Three months
Changes in Psychiatric Diagnosis of Depression
Time frame: One month
Changes in Depressive Symptoms
Time frame: One month
Results and safety
The study was stopped early (reason given: Study funds were exhausted). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2024.
- Derived from this study: PubMed 40844815Manza P, Belcher AM, Fitzsimons H, Spaderna M, Greenblatt AD, Smith HC, Derenoncourt M, Gann D, Farooq U, Kvarta MD, DiPaula BA, Merritt S, Mitic I, Zarate CA, Gould TD, Weintraub E, Kattakuzhy SM. Ketamine to enhance methadone treatment retention in patients with opioid use disorder and co-morbid depression. Am J Drug Alcohol Abuse. 2025;51(5):649-657. doi: 10.1080/00952990.2025.2541212. Epub 2025 Aug 22.
- Individual participant dataSharing planned: No
Related trials for Opioid Use Disorder
Enrolling by invitationObservational study
Development of an Interview-Informed Timeline Follow-Back (TLFB) for Opioid Use in the Era of Fentanyl
Substance Use Disorders (SUDs)
Active, not recruitingPhase 1/2
Sublingual Dexmedetomidine for Treating Opioid Withdrawal
Opioid Use Disorder, Opioid Withdrawal
Not yet recruitingPhase 4
Examining Analgesic Synergy and Efficacy in Trauma Care
Opioid Use Disorder
Not yet recruiting
Peer-led, Mobile App Supported Linkage to Opioid Use Disorder Treatment
Opioid Use Disorder
Not yet recruiting
Real World Evaluation of the Effectiveness and Implementation of a Digital Health Therapeutic for OUD
Opioid Use Disorder
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.
Annabelle Belcher, PhD principal investigator
University of Maryland, Baltimore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ketamine Hydrochloride in people with Opioid Use Disorder and Depressive Disorder, run by University of Maryland, Baltimore 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 6 inclusion and 14 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: stopped early, as of the sponsor's last update on 7 Mar 2024. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study funds were exhausted). Results are not available in the source record.
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?
Feasibility: Study Recruitment (time frame: One year). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05051449, which also lists 1 linked publication.
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 7 Mar 2024.