Modafinil - Escitalopram Study for Cocaine Dependence

NCT ID: NCT01601730

Last Updated: 2012-05-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2011-07-31

Brief Summary

The purpose of this study is to improve the efficacy of modafinil as a potential treatment for cocaine dependence.

Detailed Description

In this application, we propose an augmentation strategy intended to improve the efficacy of modafinil as a potential treatment for cocaine dependence. Recent data indicates that during chronic treatment modafinil produces substantial dopamine transporter (DAT) inhibition. Given that cocaine inhibits DA, norepenepherine (NE) and serotonin (5-HT) reuptake, it is highly likely that targeting more than one neurotransmitter system will be necessary for a medication to be effective. Assuming that this statement is true, we hypothesize that a combination pharmacotherapeutic approach that concurrently modulates multiple neurotransmitter systems will likely demonstrate a clinically significant level of efficacy above trials in which a single medication is used. The proposed approach is based on preclinical data indicating that medications that increase brain 5-HT levels reduce the effects of stimulants. We hypothesize that combining modafinil with a selective serotonin reuptake inhibitor (SSRI), which will increase synaptic levels of 5-HT, will further improve the efficacy of modafinil for reducing the effects produced by cocaine.

Specific Aims: 1) to determine the effects of treatment with oral modafinil (0 or 200 mg) plus the SSRI escitalopram (0 or 20 mg) on the subjective and reinforcing effects produced by intravenous cocaine (0 and 20 mg) in the laboratory. 2) to characterize the cocaine dependent population and the genetic basis for the rewarding effects produced by cocaine. 3) to characterize the effect of both modafinil treatment and cocaine exposure onBrain Derived Neurotrophic Factor (BDNF) in plasma. We hypothesize that both modafinil treatment and cocaine exposure will alter plasma levels of BDNF. 4 a) provide a more frequent measure of heart rate (15 sec vs. 5 minutes) and b) measure a new dependent variable, physical activity, on days with and without cocaine exposure.

Conditions

Cocaine Dependence; Cocaine Abuse; Cocaine Addiction; Substance Abuse

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching oral placebo capsules as control (Treatment 1: Modafinil 0 + Escitalopram 0).

Modafinil 200 mg + Escitalopram 20 mg

Group Type: ACTIVE_COMPARATOR

Modafinil and Escitalopram

Intervention Type: DRUG

Treatment 4: Modafinil 200 mg + Escitalopram 20 mg

Modafinil 200 mg

Group Type: ACTIVE_COMPARATOR

Modafinil

Intervention Type: DRUG

Treatment 2: Modafinil 200 mg + Escitalopram 0.

Escitalopram 20 mg

Group Type: ACTIVE_COMPARATOR

Escitalopram

Intervention Type: DRUG

Treatment 3: Modafinil 0 + Escitalopram 20 mg.

Interventions

Modafinil and Escitalopram

Treatment 4: Modafinil 200 mg + Escitalopram 20 mg

Intervention Type: DRUG

Placebo

Matching oral placebo capsules as control (Treatment 1: Modafinil 0 + Escitalopram 0).

Intervention Type: DRUG

Modafinil

Treatment 2: Modafinil 200 mg + Escitalopram 0.

Intervention Type: DRUG

Escitalopram

Treatment 3: Modafinil 0 + Escitalopram 20 mg.

Intervention Type: DRUG

Other Intervention Names

Provigil; Lexapro; Sugar pill; Provigil; Lexapro

Eligibility Criteria

Inclusion Criteria

1. Be a cocaine-dependent volunteer who is non-treatment-seeking.

2. Meet DSM-IV criteria for cocaine dependence as determined by SCID or MINI, and has provided at least one cocaine-positive urine specimen within the 2 weeks prior to enrollment.

3. Be male or female, between 18 - 55 years old.

4. Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures.

5. Female subjects must be non-nursing and postmenopausal, have had a hysterectomy, undergone tubal ligation, or have a negative pregnancy test and agree to use birth control.

6. Has medical history, physical exam, and screening laboratory results that demonstrate no contraindication to participation.

7. Be experienced with smoking or i.v. use as a route of cocaine administration.

Exclusion Criteria

1. Has a history of a medical adverse reaction to cocaine or other psychostimulants, including loss of consciousness, chest pain, cardiac ischemia, or seizure.

2. Has a current psychiatric disorder other than cocaine abuse or dependence (e.g., major depression, bipolar disorder, schizoaffective disorder, schizophrenia).

3. Meets DSM-IV criteria for dependence on other illicit drugs (e.g., methamphetamine, heroin).

4. Has received opiate-substitution therapy within 2 months of enrollment.

5. Has a current or past history of seizure disorder, including alcohol- or psychostimulant- related seizures, febrile seizures, or family history of seizure disorder.

6. Has a diagnosis of adult asthma, or chronic obstructive pulmonary disease, including a history of acute asthma within the past two years, and those with current or recent (with the past two years) treatment with an inhaled or oral b-adrenergic agonist.

7. Has had head trauma that resulted in neurological sequelae (e.g., loss of memory for greater than 5 min or that required hospitalization).

8. Has an unstable medical condition, which, in the judgment of investigators, would make participation hazardous, including, but not limited to, AIDS, acute hepatitis, active TB, unstable cardiac disease, unstable diabetes, hepatic or renal insufficiency (serum bilirubin or creatinine exceeding 1.5 the upper limit of normal, respectively).

9. Be pregnant or lactating (nursing), or a fertile woman not practicing adequate methods of contraception or planning to become pregnant within one month of conclusion of the study.

10. Has a history of suicide attempts within the past year and/or current suicidal ideation/plan.

11. Has clinically significant ECG abnormalities, including QTc interval prolongation >450 ms in men or >480 ms in women.

12. In the opinion of the PI, be expected to fail to complete the study protocol due to probable incarceration or relocation from the clinic area.

13. Has clinically significant laboratory values (outside of normal limits), in the judgment of the PI.

14. Is currently taking SSRIs, monoamine oxidase inhibitors or pimozide.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Richard De La Garza

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard De La Garza, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Locations

Michael E. DeBakey VA Medical Center

Houston, Texas, United States

Countries

United States

Other Identifiers

1RC1DA028387

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DPMC

Identifier Type: OTHER

Identifier Source: secondary_id

H-25669

Identifier Type: -

Identifier Source: org_study_id