Effects of Metformin During Nicotine Withdrawal

NCT03593538 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 824504
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the effects of a medication called metformin (Glucophage®) on smoking behavior. This medication is FDA-approved for treatment of type-2 diabetes. It is being used for research purposes in this study. Participants will be randomized to one of 3 treatment groups: low dose of metformin, high dose of metformin, or placebo.

Conditions

Smoking; HIV-1-infection

Outcome Measures

Primary Outcomes (2)

• Mood Following 24h of Smoking Abstinence

  Self-reported mood on the Positive and Negative Affect Schedule (PANAS), a 20-item Likert-format measure that assesses Positive Affect (PA; 10 items, e.g., enthusiastic, strong) and Negative Affect (NA; 10 items, e.g., distressed, upset). The minimum value for each subscale is 10 and the maximum value is 50. Higher scores indicate greater positive or negative affect.

  Day 23

• Cognitive Function Following 24h of Smoking Abstinence

  Composite score of computer-based neurocognitive tasks (N-back Working Memory Task, Stop Signal Task, Hopkins Verbal Learning Test - Revised \[HVLT-R\]) designed to test working memory and attention. A standardized z-score (mean=0, standard deviation=1) was calculated for the primary outcome for each task and an average was computed from the three z-scores. Higher scores indicated better cognitive performance.

  Day 23

Secondary Outcomes (5)

• Self-reported Smoking Behavior

  Days 7, 14, 21, and 23

• Self-reported Withdrawal Symptoms

  Days 7, 14, 21, and 23

• Self-reported Craving for Cigarettes

  Days 7, 14, 21, and 23

• Subjective Effects of Smoking

  Days 7, 14, 21, and 23

• Subjective Sensory Experience of Smoking

  Days 7, 14, 21, and 23

Study Arms (3)

Low Dose Metformin

EXPERIMENTAL

Days 1-7: Metformin 500 mg per day; Days 8-14: Metformin 500 mg and 1 Placebo capsule per day; Days 15-23: Metformin 500 mg and 2 Placebo capsules per day

Drug: Metformin; Drug: Placebo

High Dose Metformin

EXPERIMENTAL

Days 1-7: Metformin 500 mg per day; Days 8-14: Metformin 1000 mg per day; Days 15-23: Metformin 1500 mg per day

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Days 1-7: 1 Placebo capsule per day; Days 8-14: 2 Placebo capsules per day; Days 15-23: 3 Placebo capsules per day

Drug: Placebo

Interventions

Metformin DRUG

Metformin capsule

Also known as: Glucophage

High Dose Metformin; Low Dose Metformin

Placebo DRUG

Sucrose filler in gel capsules

Also known as: Placebo (for Metformin)

Low Dose Metformin; Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible subjects will be males and females:
• years of age or older who self-report smoking at least 5 cigarettes (menthol and non-menthol) per day, on average for the past 6 months.
• HIV status
• HIV-infected smokers: diagnosed with HIV infection and exhibiting viral load of less than or equal to 1000 copies/mL and CD4+ counts of greater than or equal to 200 cells/mm3 within 6 months prior to enrollment.
• HIV-uninfected smokers: no diagnosis of HIV, either via blood test or self-report.
• Must not currently be interested in quitting smoking.
• Women of childbearing potential (based on medical history) must consent to use a medically accepted method of birth control (e.g., condoms and spermicide, oral contraceptive, Depo-Provera injection, contraceptive patch, tubal ligation) or abstain from sexual intercourse during the time they are in the study and using transdermal nicotine.
• If current or past diagnosis of bipolar disorder, eligible if:
• No psychotic features
• MADRS: total score less than 8 (past 4 weeks), suicidal item score less than1 (past 4 weeks)
• Y-MRS: total score less than 8 (past 4 weeks), irritability, speech content, disruptive or aggressive behavior items score less than 3 (past 4 weeks)
• No psychiatric hospitalization or Emergency Room visits for psychiatric issues in the past 6 months
• No aggressive or violent acts or behavior in the past 6 months
• Able to communicate fluently in English.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent/HIPAA form.

You may not qualify if:

• Smoking Behavior:
• Current enrollment in a smoking cessation program, or use of other smoking cessation medications in the last month or plans to do either in the next 2 months.
• Daily use of chewing tobacco, snuff and/or snus, or electronic cigarettes.
• Alcohol/Drugs:
• Self-report current alcohol consumption that exceeds 25 standard drinks/week over the past 6 months. Subjects will be told to limit or avoid the use of alcohol while in the study to avoid any adverse reactions to the study medication.
• Current untreated and unstable diagnosis of substance dependence (eligible if past use and if receiving treatment and stable for at least 30 days). Current untreated and unstable diagnosis of substance abuse requires Study Physician approval.
• A positive urine drug screen for cocaine, amphetamines, methamphetamines, PCP, barbiturates and ecstasy (MDMA)at Intake, or any testing session (see Measures and Table 1 for details). Participants believed to have a false-positive result may continue in the study, with investigator approval.
• Medical:
• Females who self-report current pregnancy, planning a pregnancy during the study, or currently breastfeeding/lactating. All female subjects of child-bearing potential shall undergo a urine pregnancy test at the Intake, Baseline, PQ-Testing and 24-H Testing sessions.
• Current diagnosis of unstable and untreated major depression, as determined by self-report \& MINI (eligible if stable for at least 30 days).
• Current or past diagnosis of psychotic disorder, as determined by self-report or MINI.
• Suicide risk as indicated by at least one of the following on the MINI/CSSRS (the PI \&/or PM \[LCSW\] will be consulted to assess safety and determine eligibility in cases close to the eligibility cutoffs):
• Current suicidal ideation (within 30 days of enrollment)
• Two or more lifetime suicide attempts or episodes of suicidal behavior
• Any suicide attempt or suicidal behavior within 2 years of enrollment

Sponsors & Collaborators

• University of Pennsylvania: lead
• Pennsylvania Department of Health: collaborator

Study Sites (1)

Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Smoking

Interventions

Metformin

Condition Hierarchy (Ancestors)

Behavior

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Dr. Rebecca Ashare
• Organization: Perelman School of Medicine at the University of Pennsylvania

rlashare@pennmedicine.upenn.edu

2157465789

Study Officials

• Robert Schnoll, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Psychiatry

Study Record Dates

• First Submitted: June 25, 2018
• First Posted: July 20, 2018
• Study Start: April 1, 2016
• Primary Completion: March 13, 2020
• Study Completion: March 13, 2020
• Last Updated: March 26, 2021
• Results First Posted: March 26, 2021

Record last verified: 2021-03

Locations

US (1)