Effectiveness of Amantadine and Propranolol for Treating Cocaine Dependence - 2

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Institute on Drug Abuse (NIDA)
ClinicalTrials.gov Identifier:
NCT00158132
First received: September 8, 2005
Last updated: December 2, 2009
Last verified: December 2009
  Purpose

Cocaine addiction is a serious health problem with no available medical treatment for preventing relapse. Amantadine, a medication that improves muscle control, and propranolol, a medication that lowers blood pressure, may be useful in treating cocaine addiction in individuals with severe cocaine withdrawal symptoms. This study will evaluate the effectiveness of amantadine and propranolol in preventing drug relapse among cocaine addicts.


Condition Intervention Phase
Cocaine-Related Disorders
Drug: Propranolol
Drug: Amantadine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Placebo Controlled Trial of Propranolol and Amantadine for the Treatment of Cocaine Dependent Subjects With Severe Cocaine Withdrawal Symptoms

Resource links provided by NLM:


Further study details as provided by National Institute on Drug Abuse (NIDA):

Primary Outcome Measures:
  • Cocaine abstinence; measured by self-reported Time line follow-back and confirmed with cocaine urine tests. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 199
Study Start Date: September 1999
Study Completion Date: February 2006
Primary Completion Date: March 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Propranolol
Propranolol 100mg/day in 3 divided doses
Drug: Propranolol
Propranolol 100mg/day in 3 divided doses
Experimental: Amantadine
Amantadine 100mg three times daily
Drug: Amantadine
Amantadine 100mg three times daily
Experimental: Propranolol and Amantadine
Propranolol 100mg/day in 3 divided doses and Amantadine 100mg 3X's daily
Drug: Propranolol
Propranolol 100mg/day in 3 divided doses
Drug: Amantadine
Amantadine 100mg three times daily
Placebo Comparator: Placebo
Identical Placebo pills
Drug: Placebo
Placebo pills

Detailed Description:

Cocaine withdrawal symptoms are a major contributing factor for why outpatient cocaine dependence treatment programs often fail. Individuals with severe cocaine withdrawal symptoms often experience anxiety, shaking, and muscle pain. Amantadine is a medication currently used to improve muscle control, reduce shaking, and lessen stiffness. Therefore, it may help reduce the muscle pain that some cocaine addicts experience. By enhancing activity of the brain chemical dopamine, amantadine may also reduce other symptoms associated with cocaine withdrawal. Propranolol is a medication currently used to treat high blood pressure and irregular heart rhythms. It may reduce anxiety and lessen cocaine cravings in individuals addicted to cocaine. The purpose of this study is to evaluate the effectiveness of amantadine and propranolol, alone and in combination, for treating cocaine addicts with severe cocaine withdrawal symptoms.

A 2-week baseline evaluation period will be followed by an 8-week treatment phase. During the baseline evaluation, cocaine use will be measured with urine tests, three times each week. Only participants who are experiencing severe withdrawal symptoms and who use cocaine at least twice during the first 2 weeks will continue in the study. Eligible individuals will then be randomly assigned to receive amantadine alone, propranolol alone, a combination of amantadine and propranolol, or placebo. Treatments will begin at Week 3 and study visits will occur three times each week. Cocaine levels will be monitored throughout the study with urine tests.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and females, 18 to 60 years old.
  • Meets DSM-IV diagnosis criteria for cocaine dependence as determined by the Structured Clinical Interview for DSM-IV (SCID)
  • Score of at least (> or =) 22 on the Initial Cocaine Selective Severity Assessment (CSSA)
  • Lives within commuting distance of the Treatment Research Center (TRC) and the Penn/VA Center for Studies of Addiction, University of Pennsylvania
  • If female, willing to use contraception throughout the study
  • Continued use of cocaine during a two week evaluation phase prior to medication treatment as demonstrated by at least 2 new uses of cocaine documented by quantitative urine toxicology screen obtained three times weekly according to new use rules

Exclusion Criteria:

  • Meets DSM-IV/SCID diagnosis criteria for dependence on any drugs other than cocaine, marijuana, or nicotine. Cocaine dependent subjects who identify cocaine dependence as their primary addiction but who also meet criteria for alcohol dependence will be accepted as long as the alcohol dependence is not severe enough to require medications for alcohol detoxification.
  • Concomitant treatment with psychotropic medications.
  • Patients mandated to treatment based upon a legal decision or as a condition of employment. This will be assessed by the patient's self-report.
  • Current severe psychiatric symptoms (e.g., psychosis, dementia, suicidal or homicidal ideation, mania or depression requiring antidepressant medication)
  • Sensitivity to propranolol or amantadine
  • Use of any investigational medication within the past 30 days.
  • History of significant heart disease (an arrhythmia which required medication, Wolff-Parkinson -White Syndrome, angina pectoris, documented history of myocardial infarction, heart failure).
  • History of chest pain associated with cocaine use which has prompted a visit to a physician.
  • Current use of reserpine, verapamil, theophylline, trimethoprim, cimetidine, haloperidol, benzodiazepines, or anticonvulsants
  • Bronchospastic disease
  • Hyperthyroidism
  • Diabetes mellitus
  • Patients with known AIDS or other serious illnesses which may require hospitalization during the study.
  • Female subjects who are pregnant or lactating, or female subjects of child bearing potential who are not using acceptable methods of birth control. Acceptable methods of birth control include:

    1. barrier (diaphragm or condom) with spermicide
    2. intrauterine progesterone contraceptive system
    3. levonorgestrel implant
    4. medroxyprogesterone acetate contraceptive injection
    5. oral contraceptives.
  • Patients with impaired renal function as indicated by corrected creatinine clearance below 80 ml/min/70 kg as determined by the modified Cockcroft equation (CDC, 1986).
  • Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits that are clinically unacceptable to the Principal Investigator. EKG 1st degree heart block, sinus tachycardia, left axis deviation, and nonspecific ST or T wave changes are allowed; liver function tests [LFTs] <5 x ULN are acceptable). A complete list of exclusionary lab results are included in the appendix 1
  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: NCT00158132

Locations
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104 6178
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Helen M. Pettinati, Ph.D. University of Pennsylvania
  More Information

Additional Information:
Publications:
Responsible Party: Dr. Kyle Kampman, Treatment Research Center, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00158132     History of Changes
Obsolete Identifiers: NCT00128349
Other Study ID Numbers: NIDA-12756-2, P50DA012756-02, DPMC
Study First Received: September 8, 2005
Last Updated: December 2, 2009
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cocaine-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Substance-Related Disorders
Amantadine
Propranolol
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-Antagonists
Analgesics
Analgesics, Non-Narcotic
Anti-Arrhythmia Agents
Anti-Dyskinesia Agents
Anti-Infective Agents
Antihypertensive Agents
Antiparkinson Agents
Antiviral Agents
Cardiovascular Agents
Central Nervous System Agents
Dopamine Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 30, 2014