Cariprazine Effects on Brain and Behavior in Cocaine Use Disorder

ID: NCT03430544
Status: Not yet recruiting
Phase: Phase 2
Start Date: March 01, 2018
First Submitted: January 29, 2018
Last Updated: February 05, 2018
Results: N/A
Sponsors & Collaborators: Anna Rose Childress, National Institute on Drug Abuse (NIDA)
Location: United States
Conditions: Cocaine Use Disorder
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Study Description

Brief Summary

This is a phase II, randomized, single-blind, placebo-controlled study to examine whether cariprazine (1.5 or 3 mg/d) 1) alters brain and/or behavioral responses to probes of reward and inhibition and 2) decreases cocaine use in males with cocaine use disorder. Subjects will be tested as inpatients during fMRI and behavioral task sessions. Study medication will continue for 8 outpatient weeks, during which time cocaine use will be tracked. Subjects will be monitored during a 4-wk followup phase thereafter.

Detailed Description

Condition or disease Intervention/treatment Phase

Cocaine Use Disorder

Drug: Cariprazine Oral Capsule [Vraylar]
Other Names
Drug: Placebo oral capsule
Other Names
Phase 2

Tracking Information

First Submitted DateJanuary 29, 2018
Last Update Posted DateFebruary 05, 2018
Anticipated Start DateMarch 01, 2018
Anticipated Completion DateJuly 31, 2020
Anticipated Primary Completion DateJuly 31, 2020
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Primary fMRI outcome measure - BOLD signal change during visual cocaine vs. neutral cues. [Time Frame: Collected during fMRI scan 1, which takes place approximately 12-13 days after subject enrollment.]

    The primary fMRI outcome is the extracted BOLD signal change during visual stimuli reminiscent of cocaine (i.e., cocaine cues) in an a priori circuit-level ROI.

  • Primary clinical outcome measure - percentage of urines cocaine-positive or missing during outpatient phase. [Time Frame: Urines are collected 3x per week during the 8 week outpatient phase.]

    The primary clinical outcome is percentage of urines cocaine-positive or missing (assessed by urines positive for benzoylecgonine (BE), a metabolite of cocaine) throughout the outpatient treatment phase [Urines are counted as BE-positive if BE exceeds 300 ng/ml or if they are missing (no sample provided for a time point)].

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Secondary fMRI outcome measure - BOLD signal change during attempted inhibition of cue-triggered drug craving. [Time Frame: Collected during fMRI scan 2, which takes place approximately 13-14 days after subject enrollment.]

    The secondary fMRI outcome is the extracted BOLD signal change during attempted inhibition of cue-triggered drug craving in an a priori ROI .

  • Attentional bias scores [Time Frame: Completed on approximately day 14-15 after subject enrollment.]

    Attentional bias scores derived from reaction time (msec) during attentional bias task

  • Affective bias scores [Time Frame: Completed on approximately day 14-15 after subject enrollment.]

    Affective bias scores derived from reaction time (msec) during affective bias task

  • Balloon Analogue Risk Task scores [Time Frame: Completed on approximately day 14-15 after subject enrollment.]

    # of average adjusted pumps on BART

  • Go-NoGo Task scores [Time Frame: Completed on approximately day 14-15 after subject enrollment.]

    # of errors of commission

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleCariprazine Effects on Brain and Behavior in Cocaine Use Disorder
Official TitleA Randomized, Single-blind, Placebo-controlled Phase II Study to Assess the Effects of Cariprazine on Brain and Behavior in Subjects With Cocaine Use Disorder
Brief Summary

This is a phase II, randomized, single-blind, placebo-controlled study to examine whether cariprazine (1.5 or 3 mg/d) 1) alters brain and/or behavioral responses to probes of reward and inhibition and 2) decreases cocaine use in males with cocaine use disorder. Subjects will be tested as inpatients during fMRI and behavioral task sessions. Study medication will continue for 8 outpatient weeks, during which time cocaine use will be tracked. Subjects will be monitored during a 4-wk followup phase thereafter.

Detailed Description

Study TypeInterventional
Study PhasePhase 2
Estimated Enrollment
60
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Single
Primary Purpose
Treatment
Conditions
Cocaine Use Disorder
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Cariprazine Oral Capsule [Vraylar]

Cariprazine Groups (1.5 or 3mg/d): Cariprazine (VRAYLAR) capsules will be administered orally, once per day. Subjects in the 1.5mg group will receive 1 VRAYLAR capsule containing 1.5 mg cariprazine each day that study drug is administered. Subjects in the 3 mg group will be gradually titrated up to full dose: they will receive 1 VRAYLAR capsule containing 1.5mg cariprazine on the first and second days that study drug is administered and will receive 1 VRAYLAR capsule containing 3mg cariprazine each day for the rest of the medication period. The study medication period begins during the inpatient phase and ends on the last day of outpatient treatment week 8 (approx. 10 weeks total). All VRAYLAR capsules will be over-encapsulated by the University of Pennsylvania Investigational Drug Services (IDS).

Other Names
Drug: Placebo oral capsule

PLACEBO Group: Visually identical placebo capsules will be supplied by the University of Pennsylvania Investigational Drug Service, with a dosing regimen matching the cariprazine groups.

Other Names
Study Groups/Cohorts
Placebo

1.5 mg/d cariprazine

3.0 mg/d cariprazine

Study Arms
Experimental 1.5 mg/d cariprazine
Drug : Cariprazine Oral Capsule [Vraylar]
Cariprazine Groups (1.5 or 3mg/d): Cariprazine (VRAYLAR) capsules will be administered orally, once per day. Subjects in the 1.5mg group will receive 1 VRAYLAR capsule containing 1.5 mg cariprazine each day that study drug is administered. Subjects in the 3 mg group will be gradually titrated up to full dose: they will receive 1 VRAYLAR capsule containing 1.5mg cariprazine on the first and second days that study drug is administered and will receive 1 VRAYLAR capsule containing 3mg cariprazine each day for the rest of the medication period. The study medication period begins during the inpatient phase and ends on the last day of outpatient treatment week 8 (approx. 10 weeks total). All VRAYLAR capsules will be over-encapsulated by the University of Pennsylvania Investigational Drug Services (IDS).

Experimental 3.0 mg/d cariprazine
Drug : Cariprazine Oral Capsule [Vraylar]
Cariprazine Groups (1.5 or 3mg/d): Cariprazine (VRAYLAR) capsules will be administered orally, once per day. Subjects in the 1.5mg group will receive 1 VRAYLAR capsule containing 1.5 mg cariprazine each day that study drug is administered. Subjects in the 3 mg group will be gradually titrated up to full dose: they will receive 1 VRAYLAR capsule containing 1.5mg cariprazine on the first and second days that study drug is administered and will receive 1 VRAYLAR capsule containing 3mg cariprazine each day for the rest of the medication period. The study medication period begins during the inpatient phase and ends on the last day of outpatient treatment week 8 (approx. 10 weeks total). All VRAYLAR capsules will be over-encapsulated by the University of Pennsylvania Investigational Drug Services (IDS).

Placebo Comparator Placebo
Drug : Placebo oral capsule
PLACEBO Group: Visually identical placebo capsules will be supplied by the University of Pennsylvania Investigational Drug Service, with a dosing regimen matching the cariprazine groups.

Arm Intervention/Treatment
Experimental 1.5 mg/d cariprazine
Drug : Cariprazine Oral Capsule [Vraylar]
Experimental 3.0 mg/d cariprazine
Drug : Cariprazine Oral Capsule [Vraylar]
Placebo Comparator Placebo
Drug : Placebo oral capsule

Recruitment Information

Recruitment Status:Not yet recruiting
Enrollment60
Completion DateJuly 31, 2020
Eligibility Criteria: Inclusion Criteria:
1. An informed consent document voluntarily signed and dated by the subject.
2. Physically healthy males and females, aged 18-60 years old, who meet criteria for cocaine use disorder (based on DSM-V criteria) as their primary diagnosis and are voluntarily seeking treatment.
3. Females must be non-pregnant, non-lactating, and either be of non-childbearing potential (e.g., sterilized via hysterectomy or bilateral tubal ligation or at least 1 year post-menopausal) or of childbearing potential, but practicing a medically acceptable method of birth control.
4. Subject must read at or above eighth grade level and speak, understand, and write in English.
5. Intelligence quotient of ≥ 80.
6. Smoking must be a primary route of cocaine self-administration.
7. In the past 30 days, used no less than $100-worth of cocaine.
8. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
9. Available for an inpatient stay.

Exclusion Criteria:
1. Participation in a clinical trial and receipt of investigational drug(s) during 30 days prior to the research study, except as explicitly approved by the Principal Investigator.
2. Meets DSM-V criteria for moderate to severe Substance Use Disorder for any substance other than cocaine, alcohol, marijuana or nicotine as determined by the semi-structured interview. Patients with comorbid Alcohol Use Disorder will be accepted if their alcohol use disorder is not severe enough to require a medicated alcohol detoxification.
3. Meets current or lifetime DSM-V criteria for schizophrenia or any psychotic disorder, or organic mental disorder, including dementia-related psychosis.
4. Meets current DSM-V criteria for severe Major Depressive Disorder (mild and moderate MDD as well as in stable remission are allowed, if no suicidal risk and no ongoing antidepressant therapy).
5. Current comorbid GAD, Social Phobia, Specific Phobia are excluded if in current treatment and/or clinically unstable.
6. Current and/or in treatment for Panic Disorder With or Without Agoraphobia, Agoraphobia Without Panic Disorder, Post-Traumatic Stress Disorder.
7. Presence of any other psychiatric disorder that in the opinion of the PI will interfere with completion of the study or place the patient at heightened risk through participation in the study.
8. Actively suicidal or present suicidal risk or who reports a lifetime history of serious or recurrent suicidal behavior, or who has an SBQ-R total score ≥8 at Screening, and/or "yes" answers on items 4 or 5 of the C-SSRS, or in the investigator's clinical judgment presents a risk.
9. Has evidence of a history of significant active hepatitis, significant hepatocellular injury as evidenced by elevated bilirubin levels (>1.3), or other clinically significant hepatic, pulmonary, endocrine, cardiovascular, renal (creatine clearance less than 30mL/min) or gastrointestinal disease, or current AIDS, and/or clinically significant levels (over 3.5x upper limit of normal) of aspartate aminotransferase (AST), and serum alanine aminotransferase (ALT).
10. History of stroke, serious head trauma or injury causing loss of consciousness that lasted more than 3 minutes and/or associated with skull fracture or intra-cranial bleeding or abnormal MRI.
11. History of seizures.
12. Presence of magnetically active prosthetics, plates, pins, broken needles, permanent retainer, bullets, etc. in patient's body (unless a radiologist confirms that its presence is unproblematic). An x-ray may be obtained to determine eligibility.
13. Claustrophobia or other medical condition that disables the participant from lying in the MRI for approximately 60 minutes.
14. Current or prior gambling problems (assessed by subjects self-report).
15. Non-removable skin patches, at discretion of PI.
16. Has received medication that could interact adversely with cariprazine within the time of administration of study agent based on the study physician's guidance.
17. Needs treatment with any psychoactive medications (with the exception of Benadryl used sparingly, if necessary, for sleep).
18. Has demonstrated hypersensitivity to cariprazine or any ingredients in VRAYLAR capsules.
19. Currently taking a CYP3A4 inhibitor/inducer.
GenderAll
Age18 Years to 60 Years
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
United States

Administrative Information

NCT Number:NCT03430544
Other Study ID Numbers
828585
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible PartyAnna Rose Childress, University of Pennsylvania
Study Sponsor
Anna Rose Childress
Collaborators
National Institute on Drug Abuse (NIDA)
Investigators
Principal Investigator
Anna Rose Childress, PhD
University of Pennsylvania