Complementary Combination Therapy for Cocaine Dependence

NCT02538744 | Completed Phase 1 DMC

• 1 other identifier: H36362
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will assess the impact of treatment with doxazosin and modafinil, alone and in combination, on the subjective and reinforcing effects of cocaine in non-treatment-seeking, cocaine-dependent volunteers. The investigators will use a hybrid design in which participants will be randomized into two groups: placebo and doxazosin 8 mg/d. They will remain in their assigned group for the duration of the study. After titrating doxazosin to the target dose, study procedures will be completed three times, once during treatment with each dose of modafinil (0, 200, and 300 mg/d), in pseudo-random order such that 200 mg precedes 300 mg).

Conditions

Cocaine Dependence

Outcome Measures

Primary Outcomes (1)

• Subjective effects (VAS) - change from baseline over 60 minutes

  difference between the peak "High" VAS rating observed post-cocaine infusion and that observed at baseline prior to the infusion

  baseline-post cocaine (5, 15, 30, 45, and 60 minutes following each infusion)

Secondary Outcomes (2)

• heart rate change from baseline over 60 minutes

  baseline-post cocaine (continuous first 30 minutes post cocaine session and 45 and 60 min post cocaine)

• blood pressure change from baseline over 60 minutes

  baseline-post cocaine (continuous first 30 minutes post cocaine session and 45 and 60 min post cocaine)

Study Arms (2)

placebo

PLACEBO COMPARATOR

placebo po 1x/day from day -12 through 4

Drug: Doxazosin; Drug: Modafinil; Drug: cocaine; Drug: Placebo

doxazosin 8 mg

ACTIVE COMPARATOR

day -12 through -9: Doxazosin 1 mg po 1x/day day -8 through -5: Doxazosin 2 mg po 1x/day day -4 through -1: Doxazosin 4 mg po 1x/day day 1 through 4: Doxazosin 8 mg po 1x/day

Drug: Doxazosin; Drug: Modafinil; Drug: cocaine; Drug: Placebo

Interventions

Doxazosin DRUG

Participants will be randomized into two groups: placebo and doxazosin 8 mg/d. The doxazosin dose will be increased every 4 days over 11 days, starting with 1mg on the first study day and and ending with 8mg 11 days later. Participants will receive one capsule daily that will contain either placebo or doxazosin.

doxazosin 8 mg; placebo

Modafinil DRUG

After titrating doxazosin to the target dose, study procedures will be completed three times, once during treatment with each dose of modafinil (0 \[placebo\], 200, and 300 mg/d), in pseudo-random order such that 200 mg precedes 300 mg).

doxazosin 8 mg; placebo

cocaine DRUG

On the 5th day of study medication treatment participants will receive non-contingent doses of cocaine (placebo, 20, 40 mg, IV) and participate in cocaine self-administration sessions.

doxazosin 8 mg; placebo

Placebo DRUG

doxazosin 8 mg; placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Be English-speaking volunteers who are not seeking treatment at the time of the study. We require proficiency in English to ensure good communication with staff
• Be aged between 18 and 55 years
• Meet DSM-IV TR criteria for cocaine dependence using the MINI
• Have a self-reported history of using cocaine by the IV or smoked route
• Have vital signs as follows: resting pulse between 50 and 95 bpm, BP between 90-150 mmHg systolic and 45-95 mmHg diastolic
• Have hematology and chemistry laboratory tests that are within reference limits (±10%), with the following exceptions: (a) liver function tests (total bilirubin, ALT, AST, and alkaline phosphatase) \<3× the upper limit of normal and (b) kidney function tests (creatinine and BUN) \<2× the upper limit of normal
• Have a baseline ECG that demonstrates clinically normal sinus rhythm, clinically normal conduction, and no clinically significant arrhythmias
• Have a medical history and brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician and the principal investigator

You may not qualify if:

• Have any history or evidence suggestive of seizure disorder or brain injury
• Have any previous medically adverse reaction to cocaine, including loss of consciousness, chest pain, or epileptic seizure
• Meet criteria for current dependence on any drug other than cocaine or nicotine
• Have neurological or psychiatric disorders, such as:
• psychosis, bipolar illness or major depression as assessed by MINI;
• organic brain disease or dementia assessed by clinical interview;
• history of any psychiatric disorder that would require ongoing treatment or that would make study compliance difficult;
• and history of suicide attempts within the past year and/or current suicidal ideation/plan
• Have evidence of clinically significant heart disease or hypertension, as determined by the PI
• Have a family history in first-degree relatives of early cardiovascular morbidity or mortality, as determined by the PI
• Have evidence of untreated or unstable medical illness including neuroendocrine, autoimmune, renal, hepatic, or active infectious disease
• Have HIV and are currently symptomatic or are taking antiretroviral medication
• Be pregnant or nursing. Females must provide negative pregnancy urine tests upon hospital admission and at the end of study participation. Females must either be unable to conceive (i.e., surgically sterilized, sterile, or postmenopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device, condoms, or spermicide)
• Have asthma or currently use theophylline or other sympathomimetics
• Be taking a medication that potently inhibits CYP 3A4, as this enzyme metabolizes the study medications. Potent inhibitors include clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Michael Debakey VA Medical Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Doxazosin; Modafinil; Cocaine

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Prazosin; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Tropanes; Azabicyclo Compounds; Aza Compounds; Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Psychiatry Research

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: September 2, 2015
• Study Start: August 1, 2015
• Primary Completion: August 21, 2018
• Study Completion: August 21, 2018
• Last Updated: April 26, 2022

Record last verified: 2022-04

Locations

US (1)