NCT03593538: MEP

Effects of Metformin During Nicotine Withdrawal

Completed Phase 2 Results posted Last updated 26 March 2021

What this trial tests

Phase 2 trial testing Metformin in Smoking in 80 participants. Completed in 13 March 2020.

Timeline

1 April 2016

Primary endpoint
13 March 2020

13 March 2020

Quick facts

Lead sponsor	University of Pennsylvania
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	80
Start date	1 April 2016
Primary completion	13 March 2020
Estimated completion	13 March 2020
Sites	1 location across United States

Drugs / interventions tested

• Metformin (metformin) — full drug profile →
• Placebo

Conditions studied

• Smoking — all drugs for Smoking →
• HIV-1-infection — all drugs for HIV-1-infection →

Sponsor

University of Pennsylvania

Who can join

Adults 18 to 65, any sex, with Smoking or HIV-1-infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mood Following 24h of Smoking Abstinence Primary · Day 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.

Positive Affect

Group	Value	95% CI
Low Dose Metformin	36.5	± 2.5
High Dose Metformin	33.8	± 2.8
Placebo	37.9	± 2.6

Negative Affect

Group	Value	95% CI
Low Dose Metformin	14.3	± 1.3
High Dose Metformin	13.1	± 0.9
Placebo	13.9	± 1.8

Cognitive Function Following 24h of Smoking Abstinence Primary · Day 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.

Group	Value	95% CI
Low Dose Metformin	-0.018	± 0.17
High Dose Metformin	0.159	± 0.22
Placebo	-0.204	± 0.29

Self-reported Smoking Behavior Secondary · Days 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.

Day 7

Group	Value	95% CI
Low Dose Metformin	13.9	± 2.2
High Dose Metformin	8	± 1.1
Placebo	11.2	± 1.8

Day 14

Group	Value	95% CI
Low Dose Metformin	11.8	± 1.8
High Dose Metformin	8.1	± 1.0
Placebo	10.4	± 1.8

Day 21

Group	Value	95% CI
Low Dose Metformin	12.5	± 1.7
High Dose Metformin	7.4	± 0.9
Placebo	10.1	± 1.2

Day 23

Group	Value	95% CI
Low Dose Metformin	0	± 0
High Dose Metformin	0	± 0
Placebo	0	± 0

Self-reported Withdrawal Symptoms Secondary · Days 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 f

Day 7

Group	Value	95% CI
Low Dose Metformin	7.4	± 1.3
High Dose Metformin	6.3	± 0.9
Placebo	7.9	± 1.5

Day 14

Group	Value	95% CI
Low Dose Metformin	7.0	± 1.4
High Dose Metformin	6.2	± 0.8
Placebo	8.3	± 2.2

Day 21

Group	Value	95% CI
Low Dose Metformin	7.8	± 1.6
High Dose Metformin	5.5	± 0.9
Placebo	7.1	± 1.7

Day 23

Group	Value	95% CI
Low Dose Metformin	10.5	± 2.1
High Dose Metformin	8.7	± 1.3
Placebo	11.8	± 2.8

Self-reported Craving for Cigarettes Secondary · Days 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.

Day 7

Group	Value	95% CI
Low Dose Metformin	32.9	± 4.4
High Dose Metformin	26.1	± 4.2
Placebo	40.3	± 5.8

Day 14

Group	Value	95% CI
Low Dose Metformin	31.2	± 3.6
High Dose Metformin	22.3	± 3.8
Placebo	38.4	± 5.9

Day 21

Group	Value	95% CI
Low Dose Metformin	28.3	± 3.8
High Dose Metformin	21.4	± 3.3
Placebo	36.7	± 5.2

Day 23

Group	Value	95% CI
Low Dose Metformin	45.2	± 5.0
High Dose Metformin	39.9	± 4.4
Placebo	52.9	± 3.8

Subjective Effects of Smoking Secondary · Days 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.

Satisfaction (Day 7)

Group	Value	95% CI
Low Dose Metformin	4.7	± 0.4
High Dose Metformin	3.8	± 0.4
Placebo	5.8	± 0.4

Satisfaction (Day 14)

Group	Value	95% CI
Low Dose Metformin	5.0	± 0.4
High Dose Metformin	3.4	± 0.5
Placebo	5.2	± 0.4

Satisfaction (Day 21)

Group	Value	95% CI
Low Dose Metformin	4.5	± 0.4
High Dose Metformin	3.6	± 0.4
Placebo	5.0	± 0.4

Satisfaction (Day 23)

Group	Value	95% CI
Low Dose Metformin	5.1	± 0.5
High Dose Metformin	3.6	± 0.6
Placebo	4.9	± 0.6

Psychological Relief (Day 7)

Group	Value	95% CI
Low Dose Metformin	2.7	± 0.4
High Dose Metformin	2.0	± 0.2
Placebo	4.0	± 0.6

Psychological Relief (Day 14)

Group	Value	95% CI
Low Dose Metformin	3.0	± 0.5
High Dose Metformin	2.0	± 0.3
Placebo	3.5	± 0.5

Psychological Relief (Day 21)

Group	Value	95% CI
Low Dose Metformin	2.8	± 0.5
High Dose Metformin	1.9	± 0.3
Placebo	3.9	± 0.6

Psychological Relief (Day 23)

Group	Value	95% CI
Low Dose Metformin	3.2	± 0.4
High Dose Metformin	2.1	± 0.3
Placebo	3.6	± 0.5

Subjective Sensory Experience of Smoking Secondary · Days 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.

Liking scale (Day 7)

Group	Value	95% CI
Low Dose Metformin	4.6	± 0.33
High Dose Metformin	3.8	± 0.36
Placebo	5.0	± 0.33

Liking scale (Day 14)

Group	Value	95% CI
Low Dose Metformin	4.6	± 0.29
High Dose Metformin	3.6	± 0.44
Placebo	4.8	± 0.43

Liking scale (Day 21)

Group	Value	95% CI
Low Dose Metformin	4.4	± 0.37
High Dose Metformin	3.6	± 0.43
Placebo	4.7	± 0.29

Liking scale (Day 23)

Group	Value	95% CI
Low Dose Metformin	4.7	± 0.36
High Dose Metformin	3.7	± 0.43
Placebo	4.8	± 0.48

Strength scale (Day 7)

Group	Value	95% CI
Low Dose Metformin	3.9	± 0.34
High Dose Metformin	3.4	± 0.45
Placebo	3.9	± 0.42

Strength scale (Day 14)

Group	Value	95% CI
Low Dose Metformin	4.0	± 0.39
High Dose Metformin	2.9	± 0.47
Placebo	3.9	± 0.39

Strength scale (Day 21)

Group	Value	95% CI
Low Dose Metformin	3.5	± 0.43
High Dose Metformin	2.9	± 0.44
Placebo	3.5	± 0.29

Strength scale (Day 23)

Group	Value	95% CI
Low Dose Metformin	4.1	± 0.40
High Dose Metformin	3.4	± 0.51
Placebo	4.0	± 0.47

Adverse events — posted to ClinicalTrials.gov

Time frame: Through study completion, an average of 30 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Low Dose Metformin

Serious: 0/26 (0%)

Deaths: 0/26

High Dose Metformin

Serious: 0/21 (0%)

Deaths: 0/21

Placebo

Serious: 0/22 (0%)

Deaths: 0/22

Other adverse events (11 terms — click to expand)

Reaction	System	Low Dose Metformin	High Dose Metformin	Placebo
Hypertension	Vascular disorders	—	—	—
Headache	General disorders	—	—	—
Bronchitis	Respiratory, thoracic and mediastinal disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—
Heartburn	Gastrointestinal disorders	—	—	—
Increased Sweating	General disorders	—	—	—
Minor Head Injury	General disorders	—	—	—
Mouth Sores	General disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Upper Respiratory Infection	Respiratory, thoracic and mediastinal disorders	—	—	—

Data from ClinicalTrials.gov NCT03593538 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.