Ketones for Opioid Craving

June 30, 2026 updated by: Peter Manza, University of Maryland, Baltimore

Ketone Supplementation for Opioid Craving and Withdrawal

The goal of this clinical trial is to learn if ketone supplementation (KS) works to reduce craving for opioids for adults with opioid use disorder (OUD) undergoing in-patient acute withdrawal management. The main questions it aims to answer are:

  • Does KS reduce craving for opioids in patients with opioid use disorder?
  • Does KS reduce symptoms of opioid withdrawal such as low mood and pain? Researchers will compare KS to a placebo to see if KS works to reduce craving for opioids and reduce withdrawal symptoms in adults entering in-patient acute withdrawal management for opioid use disorder.

Participants will:

  • Be given KS or a placebo three (3) times daily for seven (7) days
  • Complete mood, pain tolerance, and subjective opioid withdrawal assessments

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Pennsylvania
      • Wernersville, Pennsylvania, United States, 19565
        • Caron Pennsylvania Addiction Treatment and Rehab Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18-75 years
  • Meets currents DSM-5 criteria for OUD and admitted for opioid withdrawal management treatment at Caron Treatment Center
  • Willingness to provide signed, informed consent and commit to completing the procedures in the study

Exclusion Criteria:

  • Current severe gastrointestinal (GI), liver, or other clinically significant physical disease that may interfere with the intake of the ketone supplement (e.g., sever inflammatory bowel disease, cirrhosis).
  • Currently taking (within the past two weeks) GLP-1 receptor agonist medications, e.g. semaglutide, which can interfere with the absorption of the ketone supplement
  • Currently pregnant or lactating, for people of childbearing potential
  • Judged by the principal investigator. study physician, or their designee to be an unsuitable candidate for the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment with Ketone Supplement
Participants (n=25) will receive three doses of a ketone supplement drink daily for seven days.
Dietary supplement: Treatment with Ketone Supplement
Participants (n=25) will receive three doses of a ketone supplement drink daily for seven days.
Experimental: Treatment with Placebo
Participants (n=25) will receive three doses of a placebo drink daily for seven days.
Dietary supplement: Treatment with Placebo
Participants (n=25) will receive three doses of a placebo drink for seven days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tonic Craving (FORCAST) total scores
Time Frame: Collected at baseline, and day 7
Faceted Opioid Research Craving Assessment for Substance use Treatment (FORCAST) (Opioid Craving): A 26-item assessment of tonic craving that the person reports having felt over the prior one or two weeks. Participants indicate how much they disagree or agree with each statement on a scale that ranges from 0-6, with 0 representing "strongly disagree", 3 representing "neither agree nor disagree", and 6 representing "strongly agree". Higher scores indicate higher levels of craving. The minimum score is 0, and the maximum scores for each of the subscales are as follows: Preoccupation: 24 Negative Reinforcement: 30 Positive Reinforcement: 24 Motivation: 30 Lack of control: 24 Uneasiness: 24 Maximum total score for all subscales = 156
Collected at baseline, and day 7

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain Sensitivity (Cold Pressor Test)
Time Frame: collected on day 1 and day 7
Cold Pressor Test is a well-validated measure of pain sensitivity that consistently elicits hyperalgesia in people with OUD, including those taking medications for OUD. Individuals will perform the test no later than the end of the first day of KS and again on the last day of KS. Participants plunge their dominant hand and forearm in an ice bath maintained at 5 degrees C. There are two outcomes associated with this test: pain threshold and pain tolerance. Pain threshold is the duration of time lapsed before the individual rates the sensation as painful. Pain tolerance is the duration of time the individuals keeps their arm immersed before it becomes subjectively unbearable (i.e., the individual removes their arm from the bath). Trials will be terminated if their arm is still submerged after five minutes, since pain responses on this task tend to peak by 90 seconds and diminish to below tolerance threshold within five minutes of immersion.
collected on day 1 and day 7
Desire for Drugs Questionnaire (DDQ)
Time Frame: collected on days 1-7
Desires for Drugs Questionnaire (DDQ): A 14-item assessment measured on a 7-point Likert scale with 0 representing "totally disagree" and 6 representing "totally agree" and is composed of three subscales: Desire and Intention, Negative Reinforcement, and Control. A higher score indicates a higher desire for the drug.
collected on days 1-7
Mood Ratings on a Visual Analogue Scale (VAS)
Time Frame: collected on days 1-7
A six-item validated visual analogue scale of self-report of mood. The six items represent the three primary factors of the Profile of Mood States (happy, sad, alert, tired, relaxed, nervous) Participants will see a horizontal line with 0 on the left end and 100 on the right end and will be asked "With zero (0) meaning 'Not [Happy, Sad, etc.] At All' and 100 meaning '[Happiest/Saddest, etc.] Ever' please indicate the point on the line that represents your current state."
collected on days 1-7
Subjective Opioid Withdrawal
Time Frame: Collected at baseline and days 1-7
Subjective Opioid Withdrawal Scale (SOWS): a 16-item patient self-report instrument to assess common subjective symptoms of craving and withdrawal. The SOWS uses a 0-4 scale for each item (0=not at all, 1=a little, 2=Moderately, 3=Quite a bit, 4=Extremely). Higher scores indicate higher levels of opioid withdrawal. Scores range from 0-64.
Collected at baseline and days 1-7
Chronic pain
Time Frame: collected at baseline and day 7
Graded Chronic Pain Scale (GCPS-R) is a 6-item instrument that evaluates chronic pains severity (intensity and impact on life activities). Graded scores range from 0-3 (0=Chronic Pain Absent, 1=Mild Chronic Pain, 2=Bothersome Chronic Pain, 3=High Impact Chronic Pain). Higher scores indicate higher impact of chronic pain.
collected at baseline and day 7
Mood (Positive and Negative Affect Schedule)
Time Frame: collected days 1-7
Positive and Negative Affect Schedule (PANAS) is a 20 item Likert type instrument in which participants rate the extent to which they have felt specific emotions (both positive and negative) over the past week (or since they last completed the survey). The PANAS uses a 1-5 scale (1=very slightly or not at all, 2=a little, 3=moderately, 4=quite a bit, 5=extremely) for each item, with higher scores indicating a higher extent that a participant has experienced a particular emotion. Scores range from 20-100.
collected days 1-7

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gut microbiome beta diversity
Time Frame: collected at baseline and day 7
Stool samples will be collected and the beta diversity of the gut microbiome of the experimental (ketone supplement) group will be compared to the placebo group.
collected at baseline and day 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Maryland, Baltimore

Collaborators

Caron Treatment Centers

Investigators

  • Principal Investigator: Peter Manza, PhD, University of Maryland, Baltimore

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

August 31, 2027

Study Completion (Estimated)

September 1, 2027

Study Registration Dates

First Submitted

August 13, 2025

First Submitted That Met QC Criteria

August 13, 2025

First Posted (Actual)

August 19, 2025

Study Record Updates

Last Update Posted (Actual)

July 2, 2026

Last Update Submitted That Met QC Criteria

June 30, 2026

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP-00114810

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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