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Effects of Metformin During Nicotine Withdrawal

Phase 2
Completed
Conditions
Smoking
HIV-1-infection
Interventions
Drug: Metformin
Drug: Placebo
Registration Number
NCT03593538
Lead Sponsor
University of Pennsylvania
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.

Detailed Description

There is a need for novel approaches to optimize smoking cessation treatment to help more smokers quit. Mood disturbance and cognitive deficits during nicotine withdrawal may be important treatment targets given their association with smoking relapse. In addition, factors such as HIV-1 infection may exacerbate abstinence effects on mood and cognitive deficits and thus should be measured and controlled for. The investigators hypothesize that the FDA-approved medication, metformin, will attenuate withdrawal-related mood disturbance and cognitive deficits, controlling for HIV status. Using a well-validated abstinence challenge paradigm, the investigators propose a placebo-controlled double-blind parallel arm study with one between-subjects factor of medication (low dose: 500 mg, high dose: 1500 mg, and placebo). Non-treatment seeking smokers (HIV-: n=54; 18 per group) will complete this 23 day study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
80
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Low Dose MetforminMetforminDays 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
Low Dose MetforminPlaceboDays 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
PlaceboPlaceboDays 1-7: 1 Placebo capsule per day; Days 8-14: 2 Placebo capsules per day; Days 15-23: 3 Placebo capsules per day
High Dose MetforminMetforminDays 1-7: Metformin 500 mg per day; Days 8-14: Metformin 1000 mg per day; Days 15-23: Metformin 1500 mg per day
Primary Outcome Measures
NameTimeMethod
Mood Following 24h of Smoking AbstinenceDay 23

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.

Cognitive Function Following 24h of Smoking AbstinenceDay 23

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.

Secondary Outcome Measures
NameTimeMethod
Self-reported Withdrawal SymptomsDays 7, 14, 21, and 23

The "Minnesota Nicotine Withdrawal Scale - Revised version"(MNWS_R) captures the current state of nicotine withdrawal. The scale assesses eight DSM-IV items of nicotine withdrawal including: dysphoria or depressed mood, insomnia, irritability/frustration/anger, anxiety, decreased heart rate, difficulty concentrating, restlessness, and increased appetite/weight gain. Participants rate the intensity of their symptoms on the following scale: 0 = none, 1 = slight, 2 = mild, 3 = moderate, 4 = severe and a summary score will be calculated. Withdrawal is assessed using a "past week" time reference for all time points except the 24-hr testing visit on Day 23, which uses a 24-hr time reference. The scale ranges from 0 to 32 with higher scores indicating more severe withdrawal symptoms.

Self-reported Smoking BehaviorDays 7, 14, 21, and 23

Cigarettes smoked per day as reported on the Timeline Follow-Back (TLFB). Cigarettes smoked per day is assessed using a "past week" time reference for all time points except the 24-hr testing visit on Day 23, which uses a 24-hr time reference.

Subjective Effects of SmokingDays 7, 14, 21, and 23

The Cigarette Evaluation Scale (CES), developed to assess subjective effects of smoking, is an 11-item Likert-format measure. Questions include items for nausea and dizziness, craving relief, and enjoyment of airway sensations and comprise 3 scales: satisfaction score, psychological relief score, and toxicity score. Each scale is the average of items with a minimum value of 1 and a maximum value of 7. Higher scores indicate more satisfaction, greater psychological relief, and higher subjective toxicity, respectively.

Self-reported Craving for CigarettesDays 7, 14, 21, and 23

The 10-item brief Questionnaire of Smoking Urges (QSU-B) assesses craving for cigarettes. The QSU-B contains 2 sub-scales (anticipation of reward, relief from negative affect) which are summed to create the total score. Similar to withdrawal symptoms, craving is assessed using a "past week" time reference for all time points except the 24-hr testing visit on Day 23, which will use a 24-hr time reference. Items are rated from 1 (strongly disagree) to 7 (strongly agree) and are summed to create a total score ranging from 10 to 70. Higher scores indicate higher levels of craving.

Subjective Sensory Experience of SmokingDays 7, 14, 21, and 23

The Rose Sensory Questionnaire (SQ), a 9-item Likert-format measure, assesses how much participants liked the cigarette smoked (liking scale) and how high in nicotine the cigarettes appeared to be (strength scale). The questionnaire also includes a diagram of the respiratory tract and asks participants to rate the strength of the cigarette puffs on their tongue, nose, back of mouth and throat, windpipe, and chest. Each scale is the average of items with a minimum value of 1 and a maximum value of 7. Higher scores indicate greater liking and perceived strength, respectively.

Trial Locations

Locations (1)

Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

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