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Extended-Release Naltrexone and Monthly Extended-Release Buprenorphine for Cocaine Use Disorder (CURB-2) (CURB-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05262270
Recruitment Status : Not yet recruiting
First Posted : March 2, 2022
Last Update Posted : November 9, 2022
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Madhukar H. Trivedi, MD, University of Texas Southwestern Medical Center

Brief Summary:
This is an 8-week, double-blind, randomized placebo-controlled trial of the efficacy of a combination of extended-release naltrexone (XR-NTX) and extended-release buprenorphine (XR-BUP) compared to matched placebo injections (PBO-Inj) for the treatment of cocaine use disorder (CUD).

Condition or disease Intervention/treatment Phase
Cocaine Use Disorder Drug: Extended-Release Naltrexone Drug: Extended Release Buprenorphine Drug: Placebo (PLB) Injectable Phase 2

Detailed Description:

The primary objective of this study is to assess the efficacy of XR-NTX plus XR-BUP as a combination pharmacotherapy for CUD. Approximately four hundred and twenty-six adults will be randomized into the study at 8-12 sites in the U.S. Eligibility will be determined during a maximum 21-day screening period. To document current ongoing cocaine use, participants must submit at least 2 urine samples positive for cocaine of a possible 3 tests to occur within a 10-day period during which clinic visits occur with at least 2 days between visits. In addition, participants must meet diagnostic criteria for moderate or severe CUD per DSM-5 (4 or more criteria) at screening. After screening/baseline is completed and eligibility is confirmed, participants will be randomized and begin the 1-week medication induction phase followed by the 8-week medication phase of the trial.

Participants will be randomized in a 1:1 ratio to either 1) XR-NTX + XR-BUP arm and receive injections of extended-release naltrexone (XR-NTX; as Vivitrol®) and extended-release buprenorphine (XR-BUP; as SublocadeTM), or to 2) PBO-Inj matching the timeline and delivery methods of injections for the XR-NTX + XR-BUP arm. XR-NTX or PBO-Inj injections will be provided on the day of randomization and in Weeks 3 and 6. XR-BUP or PBO-Inj injections will be provided on days 3-5 following randomization and in week 4. During the 1-week induction phase and the 8-week medication phase, participants will be asked to attend clinic twice weekly for collection of urine samples and to complete assessments as indicated on the schedule of assessments. Following the 8-week medication phase, participants will be asked to attend clinic weekly for the follow-up phase during Weeks 9-12.

Participants will be involved in the study for approximately 16 weeks, including a screening/baseline period of up to 3 weeks (i.e., 21 days), 1 week for randomization and medication induction, 8 weeks of medication, and 4 weeks of follow-up. The screening phase may differ by participant in the length of time needed to complete preliminary eligibility assessments. Confirmation of opioid-free status (urine drug screen) will take place after confirmation of eligibility and before randomization. Randomization and medication induction visit may take approximately 2 hours. Twice-weekly visits during the medication phase will range from about 20 to 90 minutes in length depending on scheduled assessments. Medication administration visits may require an additional 2 hours. Visits in the follow-up phase will take place approximately 30-60 minutes to complete. An 8-week medication period was selected based on expected time for group differences to emerge and for pragmatic issues related to medication dosing.

Enrollment is expected to take place over a period of approximately 13 months, with an approximate total of 16 months of study visits.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 426 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study intervention is three doses of 380mg XR-NTX (Weeks 0, 3 and 6) and two doses of 300mg XR-BUP (Weeks 0, 4). XR-NTX is delivered via intramuscular (IM) injection in the gluteus; XR-BUP is delivered via subcutaneous (SQ) injection in the abdomen.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: This is a double-blind, placebo-controlled study.
Primary Purpose: Treatment
Official Title: Randomized, Placebo-Controlled Trial of Extended-Release Naltrexone and Monthly Extended-Release Buprenorphine for Cocaine Use Disorder (CURB-2)
Estimated Study Start Date : January 2023
Estimated Primary Completion Date : January 2025
Estimated Study Completion Date : July 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Drug intervention (XR-NTX+XR-BUP)

The study intervention is three doses of 380mg XR-NTX (Weeks 0, 3 and 6) and two doses of 300mg XR-BUP (Weeks 0, 4).

Drug: XR-NTX XR-NTX: 3 intramuscular injections administered Week 0, 3, 6. Other Names: Extended Release Injectable Naltrexone Arm: Experimental

Drug: XR-BUP XR-BUP: 2 subcutaneous injections administered Week 0, 4. Other Names: Extended Release Injectable Buprenorphine Arm: Experimental

Drug: Extended-Release Naltrexone
XR-NTX (Extended-Release Naltrexone) doses of 380mg (Weeks 0, 3 and 6) via intramuscular (IM) injections in the gluteus.
Other Name: XR-NTX

Drug: Extended Release Buprenorphine
Extended-Release buprenorphine (XR-BUP) two doses of 300mg XR-BUP (Weeks 0, 4) via subcutaneous injections in the abdomen. Option for 100mg at Weeks 3 and 6 (if needed to alleviate side effects).
Other Name: XR-BUP

Placebo Comparator: Placebo

Matched placebo injections (PBO-Inj) for the treatment of cocaine use disorder (CUD).

Drug: Placebo (PLB) Injectable Placebo: 3 intramuscular injections administered Week 0, 3, 6. Other Names: Injectable matching (to XR-NTX) placebo Arm: Placebo Comparator - matched Placebo (PLB)

Drug: Placebo (PLB) Injectable Placebo: 2 subcutaneous injections administered Week 0, 4. Other Names: Injectable matching (to XR-BUP) placebo Arm: Placebo Comparator - matched Placebo (PLB)

Drug: Placebo (PLB) Injectable
3 doses of intramuscular injections (Week 0, 3, 6)
Other Name: Injectable matching (to XR-NTX) placebo

Drug: Placebo (PLB) Injectable
2 doses of subcutaneous injections (Week 0, 4)
Other Name: Injectable matching (to XR-BUP) placebo




Primary Outcome Measures :
  1. Proportion of Cocaine-negative UDS [ Time Frame: Week 5 up to Week 8 ]
    The primary outcome measure is the proportion of cocaine-negative UDS obtained during Weeks 5 through 8 of the medication phase as measured for the XR-NTX + XR-BUP and PBO-Inj conditions. The primary outcome (UDS) has been chosen because it is an objective measure of cocaine use and was the outcome showing significant improvement over placebo in the original CURB trial.


Secondary Outcome Measures :
  1. Number of participants who Self-report cocaine use [ Time Frame: 8 Weeks ]
    Self-report elicited through Timeline Followback (TLFB) on days of cocaine use during Weeks 0-8;

  2. Mean self reported cocaine craving score [ Time Frame: 8 Weeks ]

    Cocaine craving as measured by the Visual Analog Craving Scales (VAS) during Weeks 0-8.

    Possible scores range from 0 to 100, with higher scores indicating worse craving.


  3. Measures of safety (adverse events) [ Time Frame: 8 weeks ]
    Number and severity of adverse events reported during Weeks 0-8; Number and outcomes (non-fatal and fatal) of overdose events during Weeks 0-8

  4. Mean self reported overall functioning [ Time Frame: Week 8 ]
    Self-report overall functioning as measured by the Treatment Effectiveness Assessment (TEA) at Week 8. Possible scores range from 1 to 10 for each of the 4 domains, with higher scores indicating better outcome.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Individuals must meet all of the inclusion criteria in order to be eligible to participate in the study:

  1. Be 18 to 65 years of age;
  2. Be interested in reducing or stopping cocaine use;
  3. Meet DSM-5 criteria for moderate or severe CUD (4 or more criteria);
  4. Provide at least 2 urine samples positive for cocaine (out of a possible 3 samples) within a 10-day period collected over a maximum 21 days during screening with at least 2 days between visits;
  5. Self-report cocaine use on 18 or more days in the 30-day period prior to consent using the Timeline Follow-Back (TLFB);
  6. If female, agree to use acceptable birth control methods and have periodic urine pregnancy testing done during participation in the study unless unable to conceive (e.g., hysterectomy, post-menopause);
  7. Provide a urine sample negative for opioids and self-report no opioid use in the past 7 days on the TLFB and Prior and Concomitant Medications (PCM) assessment prior to XR-NTX induction;
  8. Be willing to comply with all study procedures and medication instructions.

Exclusion Criteria:

  1. Have a psychiatric condition that, in the judgement of the site medical clinician, would make study participation unsafe or which would prevent adherence to study procedures;

    Examples include:

    • Suicidal or homicidal ideation requiring immediate attention
    • Severe inadequately-treated mental health disorder (e.g., active psychosis, uncontrolled bipolar disorder);
  2. Have evidence of second- or third-degree heart block, atrial fibrillation, atrial flutter, prolongation of the QTc, or any other finding on the screening electrocardiogram (ECG) that, in the opinion of the site medical clinician, would preclude safe participation in the study;
  3. Have a medical condition that, in the judgement of the site medical clinician, would make study participation unsafe or which would make treatment compliance difficult. Medical conditions that may compromise participant safety or study conduct include, but are not limited to, allergy/sensitivity to study medications or diluents and the following results on clinical labs assessed during baseline/screening:

    • AST or ALT greater than 5 times the upper limit of normal
    • Total bilirubin greater than 2 times the upper limit of normal
    • Platelet count <100 x 103/μL
  4. Have a body habitus that precludes gluteal intramuscular injection of XR-NTX or abdominal SQ injection of XR-BUP in accordance with the administration equipment (needle) and procedures;
  5. Have been in a prior study of pharmacological or behavioral treatment for CUD within 6 months of study consent;
  6. Have taken an investigational drug in another study within 30 days of study consent;
  7. Have been prescribed and taken naltrexone or buprenorphine within 30 days of study consent;
  8. Be currently enrolled in formal treatment studies or addiction treatment services (behavioral or pharmacological);
  9. Be at significant clinical risk for development of serotonin syndrome with buprenorphine treatment as determined by the site medical clinician;
  10. Have a current pattern of alcohol, benzodiazepine, or other sedative hypnotic use which would preclude safe participation in the study as determined by the site medical clinician;
  11. Have a surgery planned or scheduled or otherwise medically require the use of opioid-containing medications (e.g., opioid analgesics) during the study period;
  12. Be currently in jail, prison or any inpatient overnight facility as required by court of law or have pending legal action or other situation (e.g., unstable living arrangements) in the judgement of the site investigator that could prevent participation in the study or in any study activities;
  13. If female, be currently pregnant, breastfeeding, or planning on conception;
  14. Have any condition for which, in the opinion of the site investigator or designee, study participation would not be in their best interest (including but not limited to cognitive impairment, unstable general medical condition, active psychosis) or that could prevent, limit, or confound the protocol-specified assessments.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05262270


Contacts
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Contact: Sangita Sethuram, MBA, CCRP 214-645-4357 CURB2@UTSouthwestern.edu
Contact: Angela Casey-Willingham 214-645-4357 Angela.Casey-Willingham@UTSouthwestern.edu

Sponsors and Collaborators
University of Texas Southwestern Medical Center
National Institute on Drug Abuse (NIDA)
Investigators
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Principal Investigator: Madhukar Trivedi, MD UT Southwestern Medical Center
Study Director: Geoffrey Obel, DrPh UT Southwestern Medical Center
Publications:
Center for Behavioral Health Statistics and Quality. 2019 National Survey on Drug Use and Health (NSDUH): CAI Specifications for Programming (English Version). Substance Abuse and Mental Health Services Administration, editor. Rockville, MD; 2018.

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Responsible Party: Madhukar H. Trivedi, MD, Professor of Medicine, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT05262270    
Other Study ID Numbers: STU-2021-0223
UG1DA020024 ( U.S. NIH Grant/Contract )
First Posted: March 2, 2022    Key Record Dates
Last Update Posted: November 9, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data from this study will be available to researchers on the website https://datashare.nida.nih.gov/ after the study is complete and the data is analyzed. This website will not include information that can identify individual study participants. The following information will be posted: Study protocol, reference to study publication of primary outcome, data sets (SAS and ASCII ), annotated case report forms, define file (also known as Data Dictionary), study-specific de-identification notes. Prior to downloading any study data, the user will be prompted to complete a registration agreement for data use. Users will have to register a name and valid e-mail address in order to download data and to accept their responsibility for using data in accordance with the NIDA Data Share Agreement.
Supporting Materials: Study Protocol
Clinical Study Report (CSR)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Madhukar H. Trivedi, MD, University of Texas Southwestern Medical Center:
Naltrexone
Buprenorphine
Extended release injectable Naltrexone
Extended release injectable Buprenorphine
CUD
Cocaine
Cocaine Abuse
Additional relevant MeSH terms:
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Disease
Pathologic Processes
Naltrexone
Buprenorphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists
Alcohol Deterrents