Rivastigmine and Huperzine A as Treatments for Cocaine Dependence

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by Baylor College of Medicine.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Richard De La Garza, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01030692
First received: December 10, 2009
Last updated: July 25, 2012
Last verified: July 2012
  Purpose

The purpose of this study is to determine the safety and effects of rivastigmine and huperzine A (HupA), potential treatments for cocaine abuse, when used before experimental administration of cocaine, on a number of physical and psychological measures.


Condition Intervention Phase
Cocaine Dependence
Cocaine Addiction
Cocaine Abuse
Substance Abuse
Drug: Placebo
Drug: Rivastigmine 3 mg
Drug: Huperzine A 0.4 mg
Drug: Rivastigmine 6 mg
Drug: Huperzine A 0.8 mg
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: Rivastigmine and Huperzine A as Treatments for Cocaine Dependence

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • The effects of rivastigmine or huperzine A 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 rivastigmine or HupA 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 rivastigmine or huperzine A and cocaine on subjective measures [ Designated as safety issue: No ]
    The ability of rivastigmine (3 or 6 mg, daily) or HupA (0.4 or 0.8 mg, daily), as compared to placebo, to reduce cocaine-induced craving (0, 20, and 40 mg, IV) and to reduce reinforcing effects produced by cocaine (20 mg, IV/infusion) will be measured by: 1. VAS, Adjective Scales, and MCQ; 2. Choices for cocaine vs. money in the self-administration assay.


Estimated Enrollment: 70
Study Start Date: January 2009
Estimated Study Completion Date: May 2013
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo capsules as control
Drug: Placebo
The placebo groups will receive the same dosage throughout the study.
Other Name: Sugar pill
Active Comparator: Rivastigmine 3 mg Drug: Rivastigmine 3 mg
The 3 mg rivastigmine group will receive 3 mg rivastigmine only in the evening of Day 1, 3 mg in the morning and 0 mg in the evening of Days 2-9, and 3 mg in the morning of Day 10.
Other Name: Exelon
Active Comparator: Rivastigmine 6 mg Drug: Rivastigmine 6 mg
The 6 mg rivastigmine group will receive 3 mg rivastigmine only in the evening of Day 1, 3 mg in the morning and 0 mg in the evening of Days 2-5, 3 mg in the morning and evening of Days 6-9, and 3 mg in the morning of Day 10.
Other Name: Exelon
Active Comparator: Huperzine A 0.4 mg Drug: Huperzine A 0.4 mg
The 0.4 mg HupA group will receive 0.2 mg HupA only in the evening of Day 1, 0.2 mg in the morning and evening of Days 2-9, and 0.2 mg in the morning of day 10.
Other Name: Huperzine
Active Comparator: Huperzine A 0.8 mg Drug: Huperzine A 0.8 mg
The 0.8 mg HupA group will receive 0.2 mg HupA only in the evening of Day 1, 0.2 mg in the morning and evening of Days 2-5, 0.4 mg in the morning and evening of Days 6-9, and 0.4 mg in the morning of Day 10.
Other Name: Huperzine

Detailed Description:

The purpose of this study is to evaluate the interactions between cocaine and oral rivastigmine and between cocaine and oral huperzine A (HupA).

The following Specific Aims are proposed: 1. Among cocaine-dependent, non-treatment seeking participants, to establish the ability of rivastigmine (3 or 6 mg, daily) or HupA (0.4 or 0.8 mg, daily), as compared to placebo, to reduce cocaine-induced craving (0, 20, and 40 mg, IV) and to reduce reinforcing effects produced by cocaine (20 mg, IV/infusion). Hypothesis. Relative to placebo-treated participants, treatment with rivastigmine or HupA will reduce cocaine-induced craving and choices for cocaine.

2. To determine the safety of rivastigmine and HupA in cocaine-dependent participants who receive cocaine in a laboratory setting. Hypothesis 2A. Relative to placebo-treated participants, treatment with rivastigmine or HupA will not increase the adverse events produced by cocaine. Hypothesis 2B. Relative to placebo-treated participants, treatment with rivastigmine or HupA will reduce cocaine-induced increases in heart rate and blood pressure.

3. To determine the effects of AChE inhibition on plasma levels of cocaine and cocaine metabolites. Hypothesis 3A. Relative to placebo-treated participants, treatment with rivastigmine, but not HupA, will be associated with increased plasma levels of cocaine. Hypothesis 3B. Relative to placebo-treated participants, treatment with rivastigmine, but not HupA, will be associated with increased formation of ecgonine and benzoylecgonine, and decreased formation of ecgonine methylester.

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.

Public Health Significance: Cocaine abuse is an important health problem that is associated with serious medical, psychiatric, social, and economic consequences. No medications are currently available for prevention of relapse in patients who are addicted to cocaine, and compounds such as rivastigmine and HupA are predicted to be useful for this indication. The testing of HupA is particularly exciting since it has antioxidant and neuroprotective properties that may also contribute to its efficacy as a treatment medication for cocaine dependence.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Be a cocaine-dependent volunteer who is non-treatment-seeking
  • Meets DSM-IV criteria for cocaine dependence as determined by SCID, and has provided at least one cocaine-positive urine specimen within the 2 weeks prior to enrollment
  • Be male or female, between 18 and 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 one of the birth control methods below
  • Agreeable to conditions of the study and likely to complete schedule of interventions and measures
  • Has medical history, physical exam, and screening laboratory results that demonstrate no contraindication to participation

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, including major depression, bipolar disorder, schizoaffective disorder, schizophrenia, organic brain disease, or dementia
  • Meets DSM-IV criteria for dependence to opiates, benzodiazepines, alcohol, or other sedative-hypnotics
  • Receiving opiate-substitution therapy (methadone, LAAM, or buprenorphine) within 2 mo's 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 (i.e., 21 years or older) 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 current suicidal ideation or plan as assessed by SCID or MINI interview
  • 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 on parole, probation or has any legal obligations
  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: NCT01030692

Contacts
Contact: Richard De La Garza, II, PhD (877) 228-5777 SARP@bcm.edu
Contact: Thomas F. Newton, MD (877) 228-5777 SARP@bcm.edu

Locations
United States, Texas
Michael E. DeBakey Veterans Affairs Medical Center Recruiting
Houston, Texas, United States, 77030
Contact: Richard De La Garza, II, PhD    877-228-5777      
Contact: Thomas F. Newton, MD    (877) 228-5777      
Principal Investigator: Richard De La Garza, II, PhD         
Sponsors and Collaborators
Baylor College of Medicine
Investigators
Principal Investigator: Richard De La Garza, II, PhD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Richard De La Garza, Associate Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01030692     History of Changes
Other Study ID Numbers: H-24716, 1R01DA023624, DPMC
Study First Received: December 10, 2009
Last Updated: July 25, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
Cocaine
Rivastigmine
Huperzine A

Additional relevant MeSH terms:
Cocaine-Related Disorders
Behavior, Addictive
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Compulsive Behavior
Impulsive Behavior
Cocaine
Huperzine A
Rivastigmine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Vasoconstrictor Agents
Cardiovascular Agents
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Cholinesterase Inhibitors
Enzyme Inhibitors
Cholinergic Agents
Neuroprotective Agents

ClinicalTrials.gov processed this record on August 28, 2014