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Topiramate to Reduce Cocaine Dependence

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Bankole Johnson, University of Virginia
ClinicalTrials.gov Identifier:
NCT00223626
First received: September 13, 2005
Last updated: April 17, 2012
Last verified: April 2012
  Purpose

Cocaine addiction is a serious health problem with no available medical treatment for preventing relapse. Topiramate, a medication which lowers dopamine levels, may have the ability to diminish cocaine cravings in addicts. The purpose of this study is to determine the effectiveness of topiramate in reducing cocaine's rewarding effects in individuals addicted to cocaine.


Condition Intervention Phase
Cocaine-Related Disorders
Drug: Topiramate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Lab Trials to Develop Medication for Cocaine Dependence

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Cocaine-induced mood changes [ Time Frame: measured throughout cocaine and topiramate testing sessions ] [ Designated as safety issue: No ]
  • Effects of topiramate on cognitive function [ Time Frame: measured throughout cocaine and topiramate testing sessions ] [ Designated as safety issue: No ]
  • Drug safety [ Time Frame: measured throughout cocaine and topiramate testing sessions ] [ Designated as safety issue: Yes ]
  • Cardiovascular response to cocaine (measured throughout cocaine and topiramate testing sessions) [ Time Frame: measured throughout cocaine and topiramate testing sessions ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Physiological response (measured throughout cocaine and topiramate testing sessions) [ Time Frame: measured throughout cocaine and topiramate testing sessions ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: January 2007
Study Completion Date: December 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Topiramate Drug: Topiramate
the maximum topiramate test dose is 200 mg/d.
Other Name: Topamax
Placebo Comparator: Placebo Drug: Topiramate
the maximum topiramate test dose is 200 mg/d.
Other Name: Topamax

Detailed Description:

GABA is an inhibitory neurotransmitter that is found primarily in the brain. High GABA levels result in low levels of dopamine, another neurotransmitter that is the brain's "feel good" chemical and which plays a primary role in cocaine drug addiction. Cravings for cocaine can be reduced by lowering dopamine levels. This makes topiramate, a GABA-altering medication, a potential treatment for cocaine addiction. This study will evaluate the subjective, behavioral, and physiological effects of topiramate in individuals addicted to cocaine.

Potential participants will initially attend a 4- to 6-hour screening session. This will include review of medical and drug histories, standardized psychological questionnaires, a physical exam, and blood collection. Eligible participants will then be admitted to the inpatient clinic. During the first day of experiment, participants will receive instructions and information about the study procedures. They will also undergo a physical exam, an electrocardiogram, standardized psychological questionnaires, and blood and urine collection. A single test dose of cocaine will be administered intravenously to all participants to ensure safety with continuation in the study. Vital signs will be monitored hourly throughout the day.

The experiment will last 25 days and will enroll 24 individuals addicted to cocaine. In this three-part experiment, participants will be admitted to the inpatient clinic for an 8-day study session. Following this session, they will be discharged from the clinic for a 1-week washout phase. Participants will then return to the inpatient clinic for another 8-day study session. The two study sessions will be identical. During both sessions, participants will first receive topiramate or placebo for 4 consecutive days. While continuing to receive topiramate or placebo, participants will then also receive intravenous cocaine or placebo for 3 consecutive days.Participants will be monitored by the study physician. Electrocardiograms will be used to monitor heart activity, and blood will be drawn frequently to monitor levels of cocaine and topiramate. Participants will complete standardized questionnaires several times each day to assess mood changes and cognitive function.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Meets DSM-IV-TRTM diagnostic criteria for cocaine dependence
  • Subjects must be non-treatment seeking, cocaine-dependent or cocaine-abusing individuals who report taking cocaine at least once a month
  • In generally good health as confirmed by medical history, physical examination, electrocardiogram, laboratory screening tests, and vital signs
  • Must be able to take oral medication, adhere to the medication regimens, and be willing to return to the clinic for regular study visits
  • Must be able to read and understand all instructions, rating scales, and questionnaires in English
  • Must be willing to stay overnight at the University Clinical Psychopharmacology Laboratory (UCPL)
  • Must comply with the alcohol, tobacco, and drug-free environment regulations at the UCPL
  • If female, must be postmenopausal for at least 1 year, surgically sterile, or willing to use contraception throughout the study

Exclusion Criteria:

  • History of mental illness, other than cocaine or nicotine dependence
  • History of mental retardation or neuropsychological functioning greater than 1.5 standard deviation below expected rang.
  • Clinically significant abnormalities found on the electrocardiogram
  • History of hypertension (blood pressure greater than 140/90 mm Hg) or systolic hypotension (blood pressure less than 90/75 mm Hg)
  • Resting pulse rate of greater than 90 beats per minute
  • Cerebrovascular accident or transient ischemic attack
  • Ischemic heart disease or heart attack
  • Symptomatic coronary artery disease or peripheral vascular disease
  • Cancer or history of cancer within the 5 years of study entry (other than basal cell carcinoma)
  • Kidney disease and/or impaired kidney function, as defined by an estimated creatinine clearance of 60 mL per minute
  • Gastrointestinal system disease, including active liver disease or current active hepatitis; subjects with AST and/or ALT levels greater than four times the upper limit of the normal range and/or an increased total serum bilirubin level greater than two times the upper limit of normal at screening
  • Endocrinological disorders, including thyroid disorders
  • Glaucoma
  • Gross neurological disorders, including seizure disorders and progressive or degenerative neurological disorders (e.g., multiple sclerosis)
  • History of nephrolithiasis
  • Clinically significant laboratory screening test results on hematology, chemistry, or urine analysis; up to four times above the normal range of the following will be allowed unless there is evidence of hepatocellular disease or failure: liver enzymes (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma-glutamyltransferase (GGT), blood urea nitrogen (BUN), lactate dehydrogenase (LDH)
  • Any disease or condition that compromises the function of body systems that may result in altered absorption, excess accumulation, or impaired metabolism or excretion of topiramate
  • Current use of psychoactive drugs, including sympathomimetics, caffeinated drinks in excess of 500 mg per day, and tobacco consumption of greater than 0.75 grams per day (approximately 25 cigarettes per day); non-pathological levels of alcohol consumption is permitted
  • Suicide attempt or suicidal thoughts within 30 days of study entry
  • Evidence of behavioral toxicity, including seizures, severe agitation, or psychosis
  • Be taking a medication that could interact adversely with topiramate, unless the medication is discontinued.
  • History of any severe or life-threatening medication interactions
  • Currently taking any prescribed medications for heart or cerebrovascular disease
  • Currently taking any medication with potential interactions with cocaine or topiramate, including glutamate antagonists (e.g., acamprosate), serotonin re-uptake inhibitors (e.g., fluoxetine), serotonin antagonists (e.g., ritanserin or buspirone), other antidepressants (e.g., tricyclic antidepressants or monoamine oxidase inhibitors), dopamine antagonists (e.g., haloperidol), calcium channel antagonists (e.g., isradipine), compounds with actions similar to disulfiram (Antabuse), or any carbonic anhydrase medication or medication containing triamterene
  • Previously treated with topiramate for any reason and discontinued treatment due to an adverse event or a hypersensitivity reaction to topiramate
  • Participation deemed unsafe because of precautions, warnings, or contraindications outlined in the topiramate investigator brochure and/or package insert, as determined by study investigator
  • Expected to stay in a restricted environment or awaiting imprisonment
  • Currently living in the same household as another study participant
  • Received an investigational drug or device or participated in a clinical trial in the 30 days prior to study entry
  • Employee of the investigator or study center
  • Pregnant or breastfeeding
  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: NCT00223626

Locations
United States, Virginia
University of Virginia CARE Center for Addiction Research & Education
Charlottesville, Virginia, United States, 22911
UVA CARE Richmond
Richmond, Virginia, United States, 23294
Sponsors and Collaborators
Bankole Johnson
Investigators
Principal Investigator: Bankole A. Johnson, DSc,MD.PhD University of Virginia
  More Information

Additional Information:
No publications provided

Responsible Party: Bankole Johnson, Chair of Psychiatry and Neurobehavioral Sciences, University of Virginia
ClinicalTrials.gov Identifier: NCT00223626     History of Changes
Other Study ID Numbers: 12350, R01DA012191, DPMCDA
Study First Received: September 13, 2005
Last Updated: April 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Virginia:
Cocaine Addiction
Cocaine Dependence

Additional relevant MeSH terms:
Cocaine-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Substance-Related Disorders
Cocaine
Topiramate
Anesthetics
Anesthetics, Local
Anti-Obesity Agents
Anticonvulsants
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Uptake Inhibitors
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Sensory System Agents
Therapeutic Uses
Vasoconstrictor Agents

ClinicalTrials.gov processed this record on November 19, 2014