Modafinil - Escitalopram Study for Cocaine Dependence

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Richard De La Garza, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01601730
First received: December 10, 2009
Last updated: May 16, 2012
Last verified: May 2012
  Purpose

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


Condition Intervention Phase
Cocaine Dependence
Cocaine Abuse
Cocaine Addiction
Substance Abuse
Drug: Modafinil and Escitalopram
Drug: Placebo
Drug: Modafinil
Drug: Escitalopram
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: Combination Therapy With Modafinil and Escitalopram for the Treatment of Cocaine Dependence

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • The effects of modafinil and/or escitalopram and cocaine on cardiovascular measures [ Designated as safety issue: Yes ]
    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:
  • The effects of modafinil and/or escitalopram and cocaine on subjective measures [ Designated as safety issue: No ]
    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 [ Designated as safety issue: No ]
    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.


Enrollment: 68
Study Start Date: August 2010
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Matching oral placebo capsules as control (Treatment 1: Modafinil 0 + Escitalopram 0).
Other Name: Sugar pill
Active Comparator: Modafinil 200 mg + Escitalopram 20 mg Drug: Modafinil and Escitalopram
Treatment 4: Modafinil 200 mg + Escitalopram 20 mg
Other Names:
  • Provigil
  • Lexapro
Active Comparator: Modafinil 200 mg Drug: Modafinil
Treatment 2: Modafinil 200 mg + Escitalopram 0.
Other Name: Provigil
Active Comparator: Escitalopram 20 mg Drug: Escitalopram
Treatment 3: Modafinil 0 + Escitalopram 20 mg.
Other Name: Lexapro

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01601730

Locations
United States, Texas
Michael E. DeBakey VA Medical Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Richard De La Garza, Ph.D. Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Richard De La Garza, Associate Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01601730     History of Changes
Other Study ID Numbers: H-25669, 1RC1DA028387, DPMC
Study First Received: December 10, 2009
Last Updated: May 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
Cocaine
Modafinil
Escitalopram

Additional relevant MeSH terms:
Cocaine-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Substance-Related Disorders
Armodafinil
Citalopram
Cocaine
Dexetimide
Modafinil
Anesthetics
Anesthetics, Local
Anti-Dyskinesia Agents
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antiparkinson Agents
Autonomic Agents
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Central Nervous System Stimulants
Cholinergic Agents
Cholinergic Antagonists
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Parasympatholytics
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on October 22, 2014