Clinical trial NCT00877513: Insulin Resistance in Smokers Undergoing Smoking Cessation
Official title: Insulin Resistance in Smokers Undergoing Smoking Cessation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Cardiovascular Disease
Insulin Resistance
Keywords: Smoking
Insulin resistance
Metabolic syndrome
Body fat distribution
Cigarette smoking
Lead sponsor: Charles Drew University of Medicine and Science
Sponsor class: OTHER
First posted: 2009-04-07
Enrollment: 103
Sex: ALL
Minimum age (years): 25
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Cigarette smoking increases CVD risk and worsens insulin resistance, but also contributes to weight loss; smoking cessation reduces CVD risk and improves insulin sensitivity, but also contributes to weight gain. The mechanisms that underlie these metabolic changes of cigarette smoking and smoking cessation on insulin resistance, body composition, and fat distribution are poorly understood.

Detailed description: This study is a prospective, open cohort study of smokers who undergo a smoking cessation program, and who subsequently may or may not resume smoking spontaneously. Eligible subjects will be characterized at baseline with respect to their metabolic and CVD risk profiles, body fat composition and distribution. Subjects will then undergo an intensive 8-week smoking cessation program using bupropion plus cognitive behavioral counseling. Those who successfully abstain will be reassessed. Since most individuals who quit smoking will naturally resume smoking again over time, subjects will be assessed again after an additional 4 months of follow-up when a subset of subjects will be expected to have naturally resumed smoking.

Eligibility criteria: Inclusion Criteria:

* Age 25 to 70 inclusive; any ethnicity
* Cigarette smoking for at least 3 years, at a rate of at least 1 but not more than 2 packs per day
* BMI 19 kg/m2 or greater and 40 kg/m2 or less
* Willing to enter, and be able to comply with the instructions and scheduled follow-up of a smoking cessation program

Exclusion Criteria:

* Any physical disabilities that prevent the subject from participating in the study, as determined by the investigators
* History of CVD (ventricular arrhythmias, atrial arrhythmias with a history of hemodynamic instability, unstable angina, myocardial infarction, invasive coronary revascularization, or any hospitalization for CVD within the last 3 years, NYHA Class III or IV CHF)
* Current abuse of illicit drugs or heavy ethanol use
* History or baseline laboratory evidence of diabetes mellitus
* History of chronic obstructive pulmonary disease (COPD)
* BMI \< 19 or \> 40 kg/m2
* Subjects not following a regular diet and lifestyle pattern (e.g, homeless)
* Uncontrolled hypertension (BP 170 mmHg or greater systolic or 110 mmHg or greater diastolic)
* Fasting triglycerides 700 mg/dL or greater, or LDL-cholesterol 200 mg/dL or greater
* History of chronic renal or liver disease (hepatic transaminase elevations \> 3 times the upper limit of the normal range; creatinine \> 1.5 mg/L), malignancies not currently in remission, gastrointestinal disorders that interfere with nutrition; history of malnutrition, chronic infections (including HIV), or recent (within 30 days) surgeries or hospitalizations
* Concurrent use of medications that may alter metabolic parameters (including metformin, sulfonylurea agents, thiazolidinediones, weight loss agents, androgens or systemic glucocorticoids); lipid-lowering agents and oral contraceptives will be permitted as long as formulations, dosages and adherence remain unchanged throughout the course of the study. Oral contraceptives that are started during the course of the study will require the subject to be withdrawn from the study
* Perimenopausal women experiencing irregular menses, because of changing metabolic status during the perimenopause; these patients may be included if menses have ceased for at least 6 months
* Women who are pregnant, seeking to become pregnant in the next 6 months, or who are breastfeeding
* Any history of depression, suicidality, or any contraindications to bupropion (history of seizures, anorexia or bulimia)
* Current use of nicotine replacement products (gum or patch)
* Any other factors that, in the opinion of the investigators, may interfere with the safe conduct, successful completion, or data integrity of the study

Primary outcomes:
measure: Insulin sensitivity by euglycemic hyperinsulinemic clamp
timeFrame: 8 weeks, 6 months
Secondary outcomes:
measure: Body mass index
timeFrame: 8 weeks, 4 months, 6 months
measure: Body composition
timeFrame: 8 weeks, 4 months, 6 months
measure: Body fat distribution
timeFrame: 8 weeks, 4 months, 6 months
measure: Blood pressure
timeFrame: 8 weeks, 4 months, 6 months
measure: Fasting lipid profile
timeFrame: 8 weeks, 4 months, 6 months
measure: Apolipoproteins
timeFrame: 8 weeks, 4 months, 6 months
measure: Fasting plasma glucose
timeFrame: 8 weeks, 4 months, 6 months
measure: HOMA-IR index
timeFrame: 8 weeks, 4 months, 6 months
measure: Adipokines
timeFrame: 8 weeks, 4 months, 6 months
measure: Highly-sensitive C-reactive protein
timeFrame: 8 weeks, 4 months, 6 months
measure: Morning cortisol
timeFrame: 8 weeeks, 4 months, 6 months
measure: IGF-1
timeFrame: 8 weeks, 4 months, 6 months
measure: Mean total daily caloric intake
timeFrame: 8 weeks, 4 months, 6 months
measure: Mean total daily caloric expenditure
timeFrame: 8 weeks, 4 months, 6 months
measure: Suppression of hepatic glucose production by clamp
timeFrame: 8 weeks, 6 months
measure: Resting energy expenditure by calorimetry
timeFrame: 8 weeks, 6 months
measure: Oxidative and non-oxidative glucose disposal by clamp
timeFrame: 8 weeks, 6 months
measure: Total energy expenditure under hyperinsulinemia by clamp
timeFrame: 8 weeks, 6 months
measure: Fat oxidation under hyperinsulinemia by clamp
timeFrame: 8 weeks, 6 months
measure: Fatty acid suppression under hyperinsulinemia by clamp
timeFrame: 8 weeks, 6 months
measure: Adverse events
timeFrame: 8 weeks, 4 months, 6 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Charles Drew University of Medicine and Science
state: California
Study officials:
affiliation: Charles Drew University of Medicine and Science
name: Stanley Hsia, MD
role: PRINCIPAL_INVESTIGATOR
References: