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

Cocaine Use Disorder Clinical Trial

— CURB-2  

Official title:

Randomized, Placebo-Controlled Trial of Extended-Release Naltrexone and Monthly Extended-Release Buprenorphine for Cocaine Use Disorder (CURB-2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05262270
• Other study ID #: STU-2021-0223
• Secondary ID: UG1DA020024
• Status: Recruiting
• Phase: Phase 2
• Start date: April 18, 2023
• Est. completion date: September 2026

Study information

• Verified date: April 2024
• Source: University of Texas Southwestern Medical Center
• Contact: Madhukar H Trivedi, MD
• Phone: 214-648-0188
• Email: CURB2[@]UTSouthwestern.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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. 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 426
• Est. completion date: September 2026
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Individuals must meet all of the inclusion criteria and no exclusion criteria in order to be eligible to participate in the study, including but not limited to:

Inclusion Criteria:

1. Be 18 to 65 years of age;

2. Be interested in reducing or stopping cocaine use.

3. Be willing to comply with all study procedures and medication instructions.

Exclusion Criteria:

1. Have any condition for which, in the opinion of the site investigator or designee, study participation would not be in their best interest or that could prevent, limit, or confound the protocol-specified assessments.

Related Conditions & MeSH terms

• Cocaine Use Disorder

Intervention

Drug:
• Extended-Release Naltrexone
XR-NTX (Extended-Release Naltrexone) doses of 380mg (Weeks 0, 3 and 6) via intramuscular (IM) injections in the gluteus.
• 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).
• Placebo (PLB) Injectable matched to XR-NTX
3 doses of intramuscular injections (Week 0, 3, 6)
• Placebo (PLB) Injectable matched to XR-BUP
2 doses of subcutaneous injections (Week 0, 4)

Locations

Country	Name	City	State
United States	Mountain Manor Treatment Center	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Chicago	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	UTSW Medical Center, Center for Depression Research and Clinical Care	Dallas	Texas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	UCLA Vine Street Clinic	Los Angeles	California
United States	Berman Center for Outcomes and Clinical Research at Hennepin Healthcare	Minneapolis	Minnesota
United States	Addictions Institute of Mount Sinai	New York	New York
United States	University of Texas Health San Antonio	San Antonio	Texas
United States	Center on Substance Use and Health (CSUH)	San Francisco	California
United States	Cove Behavioral Health	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

References & Publications (11)

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.

Czoty PW, Stoops WW, Rush CR. Evaluation of the "Pipeline" for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research. Pharmacol Rev. 2016 Jul;68(3):533-62. doi: 10.1124/pr.115.011668. — View Citation

dela Cruz AM, Bernstein IH, Greer TL, Walker R, Rethorst CD, Grannemann B, Carmody T, Trivedi MH. Self-rated measure of pain frequency, intensity, and burden: psychometric properties of a new instrument for the assessment of pain. J Psychiatr Res. 2014 Dec;59:155-60. doi: 10.1016/j.jpsychires.2014.08.003. Epub 2014 Aug 27. — View Citation

Kariisa M, Scholl L, Wilson N, Seth P, Hoots B. Drug Overdose Deaths Involving Cocaine and Psychostimulants with Abuse Potential - United States, 2003-2017. MMWR Morb Mortal Wkly Rep. 2019 May 3;68(17):388-395. doi: 10.15585/mmwr.mm6817a3. — View Citation

Ling W, Farabee D, Liepa D, Wu LT. The Treatment Effectiveness Assessment (TEA): an efficient, patient-centered instrument for evaluating progress in recovery from addiction. Subst Abuse Rehabil. 2012 Jan 1;3(1):129-136. doi: 10.2147/SAR.S38902. — View Citation

Ling W, Hillhouse MP, Saxon AJ, Mooney LJ, Thomas CM, Ang A, Matthews AG, Hasson A, Annon J, Sparenborg S, Liu DS, McCormack J, Church S, Swafford W, Drexler K, Schuman C, Ross S, Wiest K, Korthuis PT, Lawson W, Brigham GS, Knox PC, Dawes M, Rotrosen J. Buprenorphine + naloxone plus naltrexone for the treatment of cocaine dependence: the Cocaine Use Reduction with Buprenorphine (CURB) study. Addiction. 2016 Aug;111(8):1416-27. doi: 10.1111/add.13375. Epub 2016 Apr 21. — View Citation

Nasser AF, Heidbreder C, Liu Y, Fudala PJ. Pharmacokinetics of Sublingual Buprenorphine and Naloxone in Subjects with Mild to Severe Hepatic Impairment (Child-Pugh Classes A, B, and C), in Hepatitis C Virus-Seropositive Subjects, and in Healthy Volunteers. Clin Pharmacokinet. 2015 Aug;54(8):837-49. doi: 10.1007/s40262-015-0238-6. — View Citation

Pettinati HM, Kampman KM, Lynch KG, Suh JJ, Dackis CA, Oslin DW, O'Brien CP. Gender differences with high-dose naltrexone in patients with co-occurring cocaine and alcohol dependence. J Subst Abuse Treat. 2008 Jun;34(4):378-90. doi: 10.1016/j.jsat.2007.05.011. Epub 2007 Jul 30. — View Citation

Trivedi MH, Wisniewski SR, Morris DW, Fava M, Kurian BT, Gollan JK, Nierenberg AA, Warden D, Gaynes BN, Luther JF, Rush AJ. Concise Associated Symptoms Tracking scale: a brief self-report and clinician rating of symptoms associated with suicidality. J Clin Psychiatry. 2011 Jun;72(6):765-74. doi: 10.4088/JCP.11m06840. — View Citation

Whitfield TW Jr, Schlosburg JE, Wee S, Gould A, George O, Grant Y, Zamora-Martinez ER, Edwards S, Crawford E, Vendruscolo LF, Koob GF. kappa Opioid receptors in the nucleus accumbens shell mediate escalation of methamphetamine intake. J Neurosci. 2015 Mar 11;35(10):4296-305. doi: 10.1523/JNEUROSCI.1978-13.2015. — View Citation

Winhusen TM, Kropp F, Lindblad R, Douaihy A, Haynes L, Hodgkins C, Chartier K, Kampman KM, Sharma G, Lewis DF, VanVeldhuisen P, Theobald J, May J, Brigham GS. Multisite, randomized, double-blind, placebo-controlled pilot clinical trial to evaluate the efficacy of buspirone as a relapse-prevention treatment for cocaine dependence. J Clin Psychiatry. 2014 Jul;75(7):757-64. doi: 10.4088/JCP.13m08862. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Cocaine-negative UDS	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.	Week 5 up to Week 8
Secondary	Number of participants who Self-report cocaine use	Self-report elicited through Timeline Followback (TLFB) on days of cocaine use during Weeks 0-8;	8 Weeks
Secondary	Mean self reported cocaine craving score	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.	8 Weeks
Secondary	Measures of safety (adverse events)	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	8 weeks
Secondary	Mean self reported overall functioning	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.	Week 8