Effects of Propranolol on Responses to Drug-Related Imagery Scripts

NCT00688805 | Terminated Phase 1

• 2 other identifiers: 99990843308-DA-N433
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Relapse to drug abuse is thought to result, in many cases, from exposure to cues that trigger drug-related memories or emotional associations for example, the association between the sight of a crack pipe and a set of responses such as rapid heartbeat and desire for cocaine. This type of memory is reconsolidated (actively re-stored) each time it is reactivated; however, the reconsolidation process can be disrupted by the drug propranolol, which weakens the link between that memory and an emotional response.
• Propranolol is traditionally used to treat high blood pressure and other heart-related conditions. Researchers are interested in studying whether propranolol disrupts reconsolidation of drug-cued memories in individuals who are addicted to cocaine. Objectives: \- To examine whether propranolol can interfere with reconsolidation of cocaine-related memories and reduce cravings and drug use in substance abusers. Eligibility: \- Individuals between 18 and 55 years of age who are current cocaine users enrolled in a methadone treatment program. Design:
• The study will involve four long sessions (visits 1, 4, 6, and 14) and 10 short sessions. The short visits will be for monitoring of participants use of drugs and alcohol; the longer visits will involve more tests and lab sessions. Participants will be randomized to either the propranolol or placebo group.
• The long sessions will involve the following procedures:
• An interview session to develop a personalized drug script/cue set.
• A two-hour intervention session with baseline measures, drug administration (propranolol or placebo), and two script-guided imagery sets. This is the only administration of propranolol during the study.
• Two follow-up test sessions, 1 and 5 weeks after the intervention session.
• Participants will make brief visits to our outpatient clinic for twice-weekly monitoring of ongoing drug use via urine screens and self-report, starting 1 week before the intervention session and ending 5 weeks later.

Conditions

Cocaine Dependence

Keywords

Propanolol; Substance Abuse; Craving; Imagery; Drug Cues; Cocaine

Outcome Measures

Primary Outcomes (1)

• Drug craving

  1 hr

Secondary Outcomes (1)

• Galvanic skin response

  1 hr

Study Arms (2)

Arm 1

EXPERIMENTAL

Drug: Propranolol

Arm 2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Propranolol DRUG

40 mg given as a single oral administration in an opaque capsule

Arm 1

Placebo DRUG

matching capsule containing no active medication

Arm 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \- Age between 18 and 55 years
• \- Evidence of current cocaine use (self-report)
• \- Minimum lifetime cocaine use of one year (self-report)
• \- Minimum use of cocaine of once in the past 30 days (self-report)
• \- Enrolled in methadone maintenance

You may not qualify if:

• \- Allergy or hypersensitivity to propranolol or other beta blockers.
• \- History of: schizophrenia (or of any other DSM-IV psychotic disorder), anxiety disorders (e.g., panic disorder), or bipolar disorder.
• \- Current major depressive disorder.
• \- Current physical dependence on, or current abuse of, alcohol, benzodiazepines, or other sedative-hypnotic drugs.
• \- Cognitive impairment severe enough to preclude informed consent or valid responses on questionnaires.
• \- Pregnant; breast feeding.
• \- Impaired hepatic function with AST or ALT greater than 5x the upper limit of normal.
• \- Medical conditions that would contraindicate administration of propranolol (e.g., uncompensated congestive heart failure; pulmonary edema; asthma; COPD; history of severe allergic reactions (seasonal, environmental, food, medications, etc.); Raynaud s disease; second- or third-degree atrioventricular block; arrhythmias other than sinus arrhythmia; thyroid dysfunction; diabetes mellitus; renal impairment.
• Per the American Thoracic Society (ATS), COPD Clinical assessment is based on medical history and physical examination. Although a complete examination is indicated for all patients, these two components are specifically important for patients with suspected COPD. (ATS \& ERS, 2004) Accordingly, if medical history and physical exam suggest possible COPD the participant will be forwarded for spirometry/pulmonary function tests to aid in the diagnosis.
• \- Bradycardia (heart rate \< 60 bpm) on three consecutive readings.
• \- Systolic blood pressure \< 100 mm Hg; diastolic blood pressure \< 60 mm Hg; on three consecutive readings.
• \- Medications that could interact with propranolol either pharmacodynamically or pharmacokinetically to produce adverse effects. Such medication would include CNS depressants (e.g., barbiturates, benzodiazepines, other sedatives), antihypertensive medications (including nitrates), antiarrhythmic medications, antiseizure medications (dilantin), acetylcholinesterase inhibitors (e.g., donepezil, galantamine), aminoquinolines (antimalarial), antipsychotic medications, beta agonists, insulin, MAOIs, NSAIDs, rifamycin derivatives, rizatriptan, SSRIs, sulfonylureas, theophylline, pseudophedrine, phenylephrine, ephedrine, epinephrine, noriepinephrine, amphetamines, and some herbal supplements.
• \- Current use of beta blockers for any medical condition.

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): lead

Study Sites (1)

National Institute on Drug Abuse

Baltimore, Maryland, 21224, United States

Location

Related Publications (3)

• Abduljawad KA, Langley RW, Bradshaw CM, Szabadi E. Effects of clonidine and diazepam on the acoustic startle response and on its inhibition by 'prepulses' in man. J Psychopharmacol. 1997;11(1):29-34. doi: 10.1177/026988119701100110.

  PMID: 9097890 BACKGROUND

• Benschop RJ, Jacobs R, Sommer B, Schurmeyer TH, Raab JR, Schmidt RE, Schedlowski M. Modulation of the immunologic response to acute stress in humans by beta-blockade or benzodiazepines. FASEB J. 1996 Mar;10(4):517-24. doi: 10.1096/fasebj.10.4.8647351.

  PMID: 8647351 BACKGROUND

• Berger SP, Hall S, Mickalian JD, Reid MS, Crawford CA, Delucchi K, Carr K, Hall S. Haloperidol antagonism of cue-elicited cocaine craving. Lancet. 1996 Feb 24;347(9000):504-8. doi: 10.1016/s0140-6736(96)91139-3.

  PMID: 8596268 BACKGROUND

MeSH Terms

Conditions

Cocaine-Related Disorders; Substance-Related Disorders

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Kenzie Preston, Ph.D.

  National Institute on Drug Abuse (NIDA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 30, 2008
• First Posted: June 3, 2008
• Study Start: December 12, 2007
• Primary Completion: December 16, 2013
• Study Completion: December 16, 2013
• Last Updated: December 17, 2019

Record last verified: 2013-12-16

Locations

US (1)