- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01601730
Modafinil - Escitalopram Study for Cocaine Dependence
Combination Therapy With Modafinil and Escitalopram for the Treatment of Cocaine Dependence
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Michael E. DeBakey VA Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Be a cocaine-dependent volunteer who is non-treatment-seeking.
- 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.
- Be male or female, between 18 - 55 years old.
- Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures.
- 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.
- Has medical history, physical exam, and screening laboratory results that demonstrate no contraindication to participation.
- Be experienced with smoking or i.v. use as a route of cocaine administration.
Exclusion Criteria:
- Has a history of a medical adverse reaction to cocaine or other psychostimulants, including loss of consciousness, chest pain, cardiac ischemia, or seizure.
- Has a current psychiatric disorder other than cocaine abuse or dependence (e.g., major depression, bipolar disorder, schizoaffective disorder, schizophrenia).
- Meets DSM-IV criteria for dependence on other illicit drugs (e.g., methamphetamine, heroin).
- Has received opiate-substitution therapy within 2 months of enrollment.
- Has a current or past history of seizure disorder, including alcohol- or psychostimulant- related seizures, febrile seizures, or family history of seizure disorder.
- 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.
- Has had head trauma that resulted in neurological sequelae (e.g., loss of memory for greater than 5 min or that required hospitalization).
- 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).
- 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.
- Has a history of suicide attempts within the past year and/or current suicidal ideation/plan.
- Has clinically significant ECG abnormalities, including QTc interval prolongation >450 ms in men or >480 ms in women.
- 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.
- Has clinically significant laboratory values (outside of normal limits), in the judgment of the PI.
- Is currently taking SSRIs, monoamine oxidase inhibitors or pimozide.
Study Plan
How is the study designed?
Design Details
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
|
Matching oral placebo capsules as control (Treatment 1: Modafinil 0 + Escitalopram 0).
Other Names:
|
Active Comparator: Modafinil 200 mg + Escitalopram 20 mg
|
Treatment 4: Modafinil 200 mg + Escitalopram 20 mg
Other Names:
|
Active Comparator: Modafinil 200 mg
|
Treatment 2: Modafinil 200 mg + Escitalopram 0.
Other Names:
|
Active Comparator: Escitalopram 20 mg
|
Treatment 3: Modafinil 0 + Escitalopram 20 mg.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
---|---|
The effects of modafinil and/or escitalopram and cocaine on cardiovascular measures
|
Before and after each cocaine infusion, physiologic responses will be closely monitored using repeated HR, BP, and ECG readings.
To evaluate safety, a DSMB will meet annually and following any serious AE to examine data as well as any new published information on modafinil and/or escitalopram relevant to the project.
The number of AEs (including arrhythmias and ECG changes), changes in BP and HR, changes in cocaine PKs, and changes in mood and psychiatric symptoms (using the BSI, BDI, POMS, and BPRS) will also be assessed throughout the study.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
---|---|
The effects of modafinil and/or escitalopram and cocaine on subjective measures
|
The ability of modafinil and/or escitalopram, as compared to placebo, to reduce cocaine-induced craving will be measured by VAS and ARCI.
|
The effects of modafinil and/or escitalopram on reinforcing effects produced by cocaine
|
The ability of modafinil and/or escitalopram, as compared to placebo, to reduce reinforcing effects produced by cocaine will be measured by choices for cocaine vs. money in the self-administration assay.
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Richard De La Garza, Ph.D., Baylor College of Medicine
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Chemically-Induced Disorders
- Substance-Related Disorders
- Cocaine-Related Disorders
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Parasympatholytics
- Autonomic Agents
- Peripheral Nervous System Agents
- Muscarinic Antagonists
- Cholinergic Antagonists
- Cholinergic Agents
- Psychotropic Drugs
- Serotonin Uptake Inhibitors
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Serotonin Agents
- Antidepressive Agents
- Antidepressive Agents, Second-Generation
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 CYP3A Inducers
- Central Nervous System Stimulants
- Antiparkinson Agents
- Anti-Dyskinesia Agents
- Wakefulness-Promoting Agents
- Citalopram
- Dexetimide
- Modafinil
Other Study ID Numbers
- H-25669
- DPMC (Other Identifier: NIDA)
- 1RC1DA028387 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Substance Abuse
-
The Morton Center, Inc.National Institute on Alcohol Abuse and Alcoholism (NIAAA)UnknownAlcohol Dependence | Cannabis Dependence | Alcohol Abuse | Cannabis Abuse | Other Substance AbuseUnited States
-
National Health Promotion Associates, Inc.UnknownSubstance Use | Substance Abuse | Prescription Drug Abuse (Not Dependent)United States
-
Michael E. DeBakey VA Medical CenterUnknownAlcohol Dependence | Alcohol Abuse | Substance Abuse ProblemUnited States
-
National Health Promotion Associates, Inc.UnknownSubstance Use | Substance Abuse | Prescription Drug Abuse (Not Dependent)
-
National Institute on Drug Abuse (NIDA)CompletedDrug/Substance Abuse/Addiction | Alcohol Abuse/AddictionUnited States
-
Johns Hopkins UniversityNational Institute on Drug Abuse (NIDA)CompletedSubstance Abuse, IntravenousUnited States
-
Sheidow Consulting, Inc.Oregon Social Learning CenterCompletedSubstance Abuse ProblemUnited States
-
Penn State UniversityCompletedSubstance Abuse ProblemUnited States
-
University of California, IrvineUS Department of Veterans AffairsWithdrawn
-
Johns Hopkins UniversityNational Institute on Drug Abuse (NIDA)CompletedSubstance Abuse DisorderUnited States
Clinical Trials on Placebo
-
SamA Pharmaceutical Co., LtdUnknownAcute Bronchitis | Acute Upper Respiratory Tract InfectionKorea, Republic of
-
National Institute on Drug Abuse (NIDA)CompletedCannabis UseUnited States
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyCompletedMale Subjects With Type II Diabetes (T2DM)Germany
-
Heptares Therapeutics LimitedCompletedPharmacokinetics | Safety IssuesUnited Kingdom
-
GlaxoSmithKlineCompletedPulmonary Disease, Chronic ObstructiveUnited Kingdom, Netherlands
-
ItalfarmacoCompletedBecker Muscular DystrophyNetherlands, Italy
-
Shijiazhuang Yiling Pharmaceutical Co. LtdXuanwu Hospital, BeijingCompleted
-
GlaxoSmithKlineCompletedInfections, BacterialUnited States
-
West Penn Allegheny Health SystemCompletedAsthma | Allergic RhinitisUnited States