L-tetrahydropalmatine (l-THP) Treatment for Cocaine Use Disorder

NCT ID: NCT02139761

Last Updated: 2019-11-04

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2016-06-30

Brief Summary

Cocaine continues to be one of the most widely used substances of abuse around the world. In the US, an estimated 1.4 million individuals (0.5%) > 12 years were current (past month) cocaine users in 2011. Currently, no FDA-approved pharmacologic treatments are available for cocaine addiction; thus, this remains a serious public health problem without an effective pharmacological treatment. A promising lead towards an effective treatment comes from a recent finding that pretreatment with oral l-tetrahydropalmitine (l-THP) in rats attenuated the cocaine seeking associated with a cocaine challenge, while having no motor effects. This finding stimulated our group to test the pharmacokinetics and safety of l-THP in a phase I study of people with cocaine use. Preliminary findings show l-THP is safe and well tolerated in cocaine users, with no adverse interactions with cocaine.

This study will test the efficacy and safety of l-THP for abstinence in those with cocaine addiction in a phase II pilot study (N=24). Secondarily, we will examine the effects of these medications on craving.

Conditions

Cocaine Use

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

l-tetrahydropalmatine (l-THP)

Subjects will be dosed 30 mg BID (2 capsules total a day, total of 60mg/day), matching placebo or l-THP) (total 60 mg daily). The half-life of l-THP is about 10 hours, so subjects will reach steady state in about 2-3 days. The l-THP will be prepared at the University of Maryland School of Pharmacy to Chemistry under Good Manufacturing Practice (GMP) and standards. The identical placebo and active capsules will be manufactured and sent to the Maryland Psychiatric Research Center Pharmacy, where they will be stored, randomized and dispensed. Medication will be transported by the study staff to the participant once dispensing occurs.

Group Type: ACTIVE_COMPARATOR

l-tetrahydropalmatine (l-THP)

Intervention Type: DRUG

Subjects will be dosed 30 mg BID (2 capsules total a day, total of 60mg/day), matching placebo or l-THP) (total 60 mg daily). The half-life of l-THP is about 10 hours, so subjects will reach steady state in about 2-3 days. The l-THP will be prepared at the University of Maryland School of Pharmacy to Chemistry under Good Manufacturing Practice (GMP) and standards. The identical placebo and active capsules will be manufactured and sent to the Maryland Psychiatric Research Center Pharmacy, where they will be stored, randomized and dispensed. Medication will be transported by the study staff to the participant once dispensing occurs.

Placebo

Subjects will be dosed 30 mg BID (2 capsules total a day, total of 60mg/day), matching placebo or l-THP) (total 60 mg daily). The half-life of l-THP is about 10 hours, so subjects will reach steady state in about 2-3 days. The l-THP will be prepared at the University of Maryland School of Pharmacy to Chemistry under Good Manufacturing Practice (GMP) and standards. The identical placebo and active capsules will be manufactured and sent to the Maryland Psychiatric Research Center Pharmacy, where they will be stored, randomized and dispensed. Medication will be transported by the study staff to the participant once dispensing occurs.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subjects will be dosed 30 mg BID (2 capsules total a day, total of 60mg/day), matching placebo or l-THP) (total 60 mg daily). The half-life of l-THP is about 10 hours, so subjects will reach steady state in about 2-3 days. The l-THP will be prepared at the University of Maryland School of Pharmacy to Chemistry under Good Manufacturing Practice (GMP) and standards. The identical placebo and active capsules will be manufactured and sent to the Maryland Psychiatric Research Center Pharmacy, where they will be stored, randomized and dispensed. Medication will be transported by the study staff to the participant once dispensing occurs.

Interventions

l-tetrahydropalmatine (l-THP)

Subjects will be dosed 30 mg BID (2 capsules total a day, total of 60mg/day), matching placebo or l-THP) (total 60 mg daily). The half-life of l-THP is about 10 hours, so subjects will reach steady state in about 2-3 days. The l-THP will be prepared at the University of Maryland School of Pharmacy to Chemistry under Good Manufacturing Practice (GMP) and standards. The identical placebo and active capsules will be manufactured and sent to the Maryland Psychiatric Research Center Pharmacy, where they will be stored, randomized and dispensed. Medication will be transported by the study staff to the participant once dispensing occurs.

Intervention Type: DRUG

Placebo

Subjects will be dosed 30 mg BID (2 capsules total a day, total of 60mg/day), matching placebo or l-THP) (total 60 mg daily). The half-life of l-THP is about 10 hours, so subjects will reach steady state in about 2-3 days. The l-THP will be prepared at the University of Maryland School of Pharmacy to Chemistry under Good Manufacturing Practice (GMP) and standards. The identical placebo and active capsules will be manufactured and sent to the Maryland Psychiatric Research Center Pharmacy, where they will be stored, randomized and dispensed. Medication will be transported by the study staff to the participant once dispensing occurs.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• men or non-pregnant/non-nursing women between the ages of 18 and 50 years
• meeting criteria for DSM-5 cocaine use disorder
• self-reported cocaine use (intranasal, IV or smoked) averaging at least weekly for the prior six months positive urine drug test for cocaine in the prior month
• HIV seronegative
• EKG without clinically significant abnormality
• normal blood pressure (systolic: 90-140 mmHg; diastolic: 50-90 mmHg) and resting heart rate (60-90 bpm)
• ability to adhere to the study restrictions and examination schedule
• women with reproductive potential must agree to the use of one of the following birth control methods (oral contraceptives, condom with spermicide, diaphragm, or intrauterine device) during the study and for 2 weeks after last medication dose.

Exclusion Criteria

• participation in any investigational drug trial or clinical drug trial within 45 days before study entry
• history of clinically significant adverse reaction or hypersensitivity to cocaine or l-THP
• inability to communicate or co-operate with the investigators
• currently taking any prescribed psychoactive medication, e.g., anti- depressant, anti-psychotic, or mood stabilizer
• current clinically significant medical problem that might interfere with safe study participation. This includes pheochromocytoma, untreated hyperthyroidism, dehydration, fever, coronary artery disease, uncorrected congenital heart defect, seizures, electrolyte imbalance, uncontrolled diabetes mellitus, porphyria variegate, superventricular tachycardia, atrial fibrillation, cardiomyopathy, or uncontrolled hypertension.
• current Axis I Major Depression, Schizophrenia, or Bipolar Disorder.
• score below 10/12 on the Evaluation to Sign Consent (ESC)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Deanna Kelly

Deanna L. Kelly Pharm.D., BCPP

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Deanna L Kelly, Pharm.D, BCPP

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

Maryland Psychiatric Research Center

Catonsville, Maryland, United States

Countries

United States

Other Identifiers

HP-00059193

Identifier Type: -

Identifier Source: org_study_id