Cocaine Dependence
Conditions
Keywords
cocaine, dependence, pharmacotherapy
Brief summary
The purpose of this study is to see if a drug called Candesartan will help to reduce use of cocaine.
Detailed description
The noradrenergic system may play an important role in cocaine addiction in humans. Angiotensin II (Ang II) is known to enhance noradrenergic activity, which contributes to effects on blood pressure and sympathetic nervous system responses to stress. Inhibition of Ang II has been shown to reduce cravings for stimulants, including cocaine and methamphetamine. This clinical trial among 75 cocaine-dependent subjects is designed to test the efficacy of the Angiotensin II receptor antagonist, Candesartan, for treatment of cocaine dependence. The results of this study will provide medical safety and efficacy data, and will guide future pharmacotherapy trials using this class of medications for cocaine addiction. This 8-week trial includes a 1-week titration of the medication and 7-weeks of full dose medication (weeks 2-8), with all subjects receiving the active agent. At the conclusion of the trial, subjects who wish to be referred to an appropriate treatment program or treatment research program will be assisted with a referral.
Interventions
DRUGCandesartan with CBT
8 mg, po (by mouth)
OTHERPlacebo with CBT
Sponsors
National Institute on Drug Abuse (NIDA)
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
To be eligible for study entry, all subjects must satisfy the following criteria: 1. Age 18 to 64 years inclusive; 2. Females either must be of non-child bearing potential (i.e., surgically sterilized or postmenopausal) or must be using adequate contraception, have a negative pregnancy test, and must agree to continue to use such precautions for the duration of the study. 3. Meets Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV-TR) criteria for a principal diagnosis of cocaine dependence as confirmed by the MINI and/or as per PI/study investigator's examination of the patient during screening. (Per DSM-IV-TR, principal diagnosis is the condition that is the primary target of treatment at the time of presentation); 4. Motivated to discontinue or reduce cocaine use during the period of the study, as evidenced both by the judgment of the Investigator or designee and by the subject's compliance level with the requirement for attendance at clinic visits such that the urine sample requirements for inclusion criteria #6 is fully met; 5. Has a positive pattern of cocaine usage as determined by provision of at least one cocaine positive urine sample (benzoylecgonine (BE) level at least 300 ng/ml) during the screening period; typically conducted over a 7-14 day period. 6. In good general health as determined by self-reported and/or computer-based medical history, general clinical examination, and laboratory tests; 7. Has provided written informed consent. 8. Are cooperative, willing and able to participate and adhere to the protocol requirements
Exclusion criteria
Subjects will be excluded from the study if one or more of the following statements are applicable: 1. Subject is taking angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin, in Lotrel), captopril (Capoten, in Capozide), enalapril (Vasotec, in Lexxel, in Vaseretic), fosinopril (Monopril), lisinopril (Prinivil, Zestril, in Prinzide, in Zestoretic), moexipril (Univasc, in Uniretic), perindopril, (Aceon), quinapril (Accupril, in Accuretic, in Quinaretic), ramipril (Altace), and trandolapril (Mavik, in Tarka); lithium (Eskalith Controlled-Release, Eskalith, Lithobid); 2. Subject is on psychotropic medications, an MAOI, or an opiate antagonist; 3. Subject is currently taking a dopaminergic, dopamine-blocking, dopamine-modulating, or other central dopamine-altering drug (e.g., antipsychotic drugs); a monoamine oxidase inhibitor (MAOI); or an opiate antagonist; 4. Subject has an unstable medical, neurologic, or psychiatric illness that would interfere with the subject's safety, ability to participate in the study, or the interpretability of data. Subjects who meet the DSM-IV-R criteria for psychosis, schizophrenia, bipolar disorder or clinically significant suicidal ideation as assessed by the PI/study investigator and/or the MINI will be excluded. Subjects who have been taking stable doses of antidepressants for at least 3 months at the time the consent is signed will be allowed onto the study unless those antidepressants are of the types specified under
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| # of Participants With Presence of Cocaine Metabolites Via Urinalysis | thrice weekly, baseline thru week 8 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| # of Participants Retained in Study | 8 weeks | — |
| # of Participants With Adverse Events | 8 weeks | Candesartan will be well tolerated without significant side effects. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Candesartan w Cognitive Behavior Therapy Titration up to 8mg wk 1-4. Continue on 8mg thru wk 8. CBT optional thru study.
Candesartan with CBT: 8 mg, po (by mouth) | 20 |
| Placebo w Cognitive Behavior Therapy Sugar pill to mimic Candesartan for study duration. CBT optional thru study.
Placebo with CBT | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | Candesartan w Cognitive Behavior Therapy | Placebo w Cognitive Behavior Therapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 10 Participants | 30 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 20 Participants | 10 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 10 |
| other Total, other adverse events | 0 / 20 | 0 / 10 |
| serious Total, serious adverse events | 0 / 20 | 0 / 10 |
Outcome results
Primary
# of Participants With Presence of Cocaine Metabolites Via Urinalysis
Time frame: thrice weekly, baseline thru week 8
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Candesartan w Cognitive Behavior Therapy | # of Participants With Presence of Cocaine Metabolites Via Urinalysis | 20 participants |
| Placebo w Cognitive Behavior Therapy | # of Participants With Presence of Cocaine Metabolites Via Urinalysis | 10 participants |
Secondary
# of Participants Retained in Study
Time frame: 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Candesartan w Cognitive Behavior Therapy | # of Participants Retained in Study | 5 participants |
| Placebo w Cognitive Behavior Therapy | # of Participants Retained in Study | 0 participants |
Secondary
# of Participants With Adverse Events
Candesartan will be well tolerated without significant side effects.
Time frame: 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Candesartan w Cognitive Behavior Therapy | # of Participants With Adverse Events | 0 participants |
| Placebo w Cognitive Behavior Therapy | # of Participants With Adverse Events | 0 participants |