Varenicline for the Treatment of Cannabis and Tobacco Use Disorders in Veterans (Vet Cat)

• ClinicalTrials.gov Identifier: NCT05294263
• Recruitment Status: Not yet recruiting
• First Posted: March 24, 2022
• Last Update Posted: January 17, 2023
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

Tracking Information

• First Submitted Date: February 9, 2022
• First Posted Date: March 24, 2022
• Last Update Posted Date: January 17, 2023
• Estimated Study Start Date: March 1, 2023
• Estimated Primary Completion Date: December 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 14, 2022)

• Number of cannabis using day as reported on Timeline Followback [ Time Frame: Weeks 6-12 ]
  Number of cannabis using days as self-reported on TLFB
• Average number cigarettes smoked per day as reported on Timeline Followback [ Time Frame: Weeks 6-12 ]
  Average number of cigarettes smoked per day as self-reported on TFLB

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided

Current Other Pre-specified Outcome Measures (submitted: March 14, 2022)

Number of participants engaged in study visits and treatment [ Time Frame: Week 12 ]

Participants will be considered retained if they are actively engaged in study visits and treatment at Week 12

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Varenicline for the Treatment of Cannabis and Tobacco Use Disorders in Veterans
• Official Title: Varenicline for Comorbid Tobacco and Cannabis Use in Veterans
• Brief Summary: After initial eligibility screening, Veterans who use both cannabis and tobacco will be randomly assigned to receive either varenicline (Chantix) or placebo for 12 weeks. Participants will attend weekly visits to provide breath and urine samples for testing, fill out questionnaires, and meet with study staff about medication compliance.

Detailed Description

Screening and Eligibility Assessment. Individuals will be screened by the research study intake coordinator. An initial pre-screen focused on inclusion/exclusion psychiatric diagnoses, medical status, current medication regimen, and ability and willingness to commit to completion of study procedures will be used to initially determine potential study eligibility. Interested individuals will be given a full description of the study procedures and asked to read and sign an IRB-approved informed consent form before participating in a detailed, comprehensive screening and assessment phase.

Diagnostic/Descriptive Assessment. The MINI International Neuropsychiatric Interview (MINI) will be used to assess psychiatric and substance use diagnoses. A medical history and physical exam will be conducted to ensure that the individual is eligible to participate. In the event an individual is found to be ineligible to participate in this research protocol, he or she will be given an appropriate referral for further medical care or to an appropriate treatment program. If found eligible, a randomization visit will be scheduled, and ongoing cannabis and tobacco use will be tracked between initial assessment and randomization.

Treatment Assignment. Eligible individuals will be randomized to receive varenicline or matching placebo in a 1:1 manner utilizing a stratified random block design with block sizes of 2, 4 and 6. To achieve treatment balance, randomization will be stratified by gender and presence of comorbid psychiatric conditions (depression, PTSD, etc.) as both have been shown to modify cannabis use. The randomization allocation schedule will be developed by the study statistician (Partially blinded, A/B treatment) and all study staff, the investigative team and participants will remain blinded to study assignment until study completion or an otherwise medical necessity. The study randomization will be reviewed by the study statistician (partially blinded) on a regular basis to ensure that the schedule is being implemented according to plan. Final treatment assignment (A/B) and dispensing will be performed by the VA Investigational Pharmacy, a centralized research pharmacy that manages clinical trial medications. Varenicline will be provided at the standard recommended dose of 0.5mg daily for three days, then 0.5mg twice daily for four days, and then 1mg twice daily for the remainder of the 12-week treatment period. Medication (varenicline and matching placebo capsules) will be compounded by Pitt Street Pharmacy, a local pharmacy that has been utilized previously by VA investigators. Dr. McRae-Clark holds an IND from the FDA for the use of varenicline in individuals with cannabis use disorder.

Medication Management. Medication Management (MM) is a common-sense, generalizable approach to encourage adherence to medication specifically, and to a treatment plan in general. Once a week, participants will be seen for a brief MM session. Sessions will be focused on (a) developing and maintaining rapport, (b) reviewing AEs and concomitant medications, and (c) discussing progress with medication adherence and cannabis reduction/abstinence. These sessions provide an opportunity to address challenges and help participants devise strategies for success.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Double Blind Placebo Controlled Trial: . Eligible individuals will be randomized to receive varenicline or matching placebo in a 1:1 manner utilizing a stratified random block design with block sizes of 2, 4 and 6.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition

• Tobacco Use Disorder
• Cannabis Use Disorder

Intervention

• Drug: Varenicline
  Varenicline is a selective nACHr partial agonist of the 4 2 subtype and a full agonist of the 7 subtype
  Other Name: Chantix
• Drug: Placebo
  Matching, inactive medication

Study Arms

• Experimental: Varenicline
  Varenicline will be provided at the standard recommended dose of 0.5mg daily for three days, then 0.5mg twice daily for four days, and then 1mg twice daily for the remainder of the 12-week treatment period.
  Intervention: Drug: Varenicline
• Placebo Comparator: Placebo
  Matching placebo will be administered over the 12-week period.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: March 14, 2022): 138
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2025
• Estimated Primary Completion Date: December 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Meet DSM-5 criteria for cannabis use disorder and use cannabis at least 3 days per week in the last 30 days.
• Meet DSM-5 criteria for tobacco use disorder and smoke at least five cigarettes per day.
• Males and female Veterans aged 18 and over.
• Be interested in quitting or reducing cannabis and tobacco use.
• If female and of childbearing potential, must agree to use acceptable methods of birth control for the duration of the trial.
• Must consent to random assignment, and be willing to commit to medication ingestion.
• Must be able to read and provide informed consent.
• Must have body weight >110lbs (50kg) and have BMI between 18 and 35 kg/m2
• Must function at an intellectual level and have knowledge of the English language to sufficiently allow for accurate completion of assessments.

Exclusion Criteria:

• Women who are pregnant, nursing, or plan to become pregnant during the course of the study.
• Individuals with severe renal impairment.
• Lifetime history of DSM-5 Bipolar I or II Disorder, Schizophrenia or other psychotic disorder. Stably treated MDD, Dysthymia, GAD, Social Phobia, PTSD, and Specific Phobia diagnoses are acceptable (i.e. same dose of medication/psychotherapy has been prescribed for at least 2 months prior to screening and no changes in current medication/psychotherapy expected during course of the trial).
• Suicidal ideation or behavior within the past 6 months. Subjects who are believed to be at suicidal (answers 'yes' on questions 4 or 5 of C-SSRS) or homicidal risk will be referred to assessment by a mental health professional.
• Concomitant use of psychotropic medications, with the exception of stable doses (defined as no dosing adjustments in the past two months) of non-MAO-I antidepressants, non-benzodiazepine anxiolytics, and ADHD medications.
• Current use of medications prescribed for mania or psychosis (these medications may be allowed if used for other indications)
• Current use of bupropion, amitriptyline or nortryptiline or other medication known to have drug interactions with varenicline
• Moderate or severe non-cannabis substance use disorders within the past 60 days with the exception of tobacco use disorder.
• Individuals taking an investigational agent within the last 30 days before baseline visit.
• Individuals with clinically significant medical disorders or lab abnormalities.
• Individuals with clinically significant cardiovascular disease in the past 6 months (e.g., myocardial infarction, CABG, PTCA, or severe or unstable angina).
• Individuals with clinically significant cerebrovascular disease in the past 6 months such as TIA, CVA, or stroke
• Hypersensitivity to varenicline.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Aimee L Mcrae-Clark, PharmD; (843) 792-5216; Aimee.McRae-Clark@va.gov

Contact: Lisa Nunn; (843) 792-0476; jenkinli@musc.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05294263
• Other Study ID Numbers: NURA-004-21S; I01CX002357 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: VA Office of Research and Development
• Original Responsible Party: Same as current
• Current Study Sponsor: VA Office of Research and Development
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Aimee L. Mcrae-Clark, PharmD; Ralph H. Johnson VA Medical Center, Charleston, SC

• PRS Account: VA Office of Research and Development
• Verification Date: January 2023