The Effectiveness of Smoking Cessation in Prediabetic Smokers

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Taiwan University Hospital
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT01926041
First received: August 6, 2013
Last updated: April 13, 2014
Last verified: April 2014
  Purpose

Smoking is one of major risk factor for incident type 2 diabetes mellitus (DM), and smoking cessation can improve insulin resistance. Nowadays, the second-generation cessation program in Taiwan brings higher accessibility. However, there is little evidence on the long-term health outcomes of smoking cessation for the prediabetics in the community.

This project is of five-year design. The investigators plan to recruit at least 596 prediabetic smokers and 600 prediabetic non-smokers from communities. Initially, a cross-sectional analysis will be performed to investigate the physiological and psychological characteristics in prediabetic smokers. All participants are provided with standardized diet, lifestyle education, and skills of body weight self-management, with prospective follow-up every 3-6 months. Individuals may voluntarily attend smoking cessation program. Cox regression models and Kaplan-Meier methods will be used to investigate the effectiveness of the smoking cessation and body weight self-management in prediabetics regarding new-onset DM risk, glucose control, cardiovascular events, chronic kidney diseases, chronic hepatitis or cirrhosis, malignancy, and the relevant physiological and psychological parameters of interest.


Condition Intervention
Diabetes Mellitus
Cigarette Smoking
Prediabetes
Other: Smoking cessation
Behavioral: Self-management

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Community-based Pilot Study of the Effectiveness of Smoking Cessation for Prediabetes

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Diagnosis of diabetes mellitus by ADA criteria [ Time Frame: at least 3 years (from Aug 1, 2013) ] [ Designated as safety issue: No ]
    The primary outcome is DM, defined as having repeatedly at least one of the following criteria: 1) plasma glucose ≥126 mg/dL (7.0 mmol/L) in the fasting state; 2) plasma glucose ≥200 mg/dL (11.1 mmol/L) randomly with hyperglycemic symptoms or two hours after a 75-g oral glucose load; 3) A1C ≥6.5%;20 or under medications for physician-diagnosed DM.


Secondary Outcome Measures:
  • A1C Change and Regression to Normoglycemia [ Time Frame: at least 3 years (from Aug 1, 2013) ] [ Designated as safety issue: No ]
    Normoglycemia is defined as having all the following for over 3 months: 1) plasma glucose <100 mg/dL (5.6 mmol/L) in the fasting state; 2) plasma glucose <140 mg/dL (7.8 mmol/L) two hours after a 75-g oral glucose load; 3) A1C <5.7%, in the absence of diabetic medications.

  • Diagnoses of cardiovascular events [ Time Frame: at least 3 years (from Aug 1, 2013) ] [ Designated as safety issue: No ]
    by specialists

  • Chronic kidney disease progression [ Time Frame: at least 3 years (from Aug 1, 2013) ] [ Designated as safety issue: No ]
    including change in eGFR and microalbuminuria

  • Chronic hepatitis or cirrhosis progression [ Time Frame: at least 3 years (from Aug 1, 2013) ] [ Designated as safety issue: No ]
    confirmed by ultrasonography or advanced image or pathology studies

  • Malignancy incidence [ Time Frame: at least 3 years (from Aug 1, 2013) ] [ Designated as safety issue: No ]
    confirmed by national cancer registry system


Other Outcome Measures:
  • All-cause mortality [ Time Frame: at least 3 years (from Aug 1, 2013) ] [ Designated as safety issue: No ]
    Deaths are ascertained by computer linkage to the national death registry (death certificates were created by the Department of Health, Taiwan) using ID numbers and these death certificates have been validated.


Estimated Enrollment: 1200
Study Start Date: August 2013
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Smoking cessation
Participants in smoking cessation program will receive counseling from a physician and a nurse, educational materials explaining smoking cessation techniques, and prescriptions. Drugs are administered according to the manufacturer's directions, and a 1- to 4-week supply of medicine is prescribed at every clinic visit. Users can receive their medications for a course of 8 weeks in the following 90 days, with a maximum of two courses within one year (www.hpa.gov.tw). During the therapy course, physicians are allowed to adjust varenicline dosages according to tolerability.
Other: Smoking cessation
Each participant also receives counseling for individualized smoking cessation techniques at each visit. We do not prescribe the nicotine replacement therapy because it may induce insulin resistance and confound our study outcome. Bupropion is not available in our institutions and not prescribed. Varenicline users are encouraged to set either a fixed quit date or a flexible quit date. Varenicline is administered according to the manufacturer's directions, and a 1- to 4-week supply of medicine is prescribed at every clinic visit. At the end of the program, smoking status is assessed by self-reported 7-day point-prevalence abstinence, confirmed by a breath CO level of less than 3 ppm. We provide incentives to help minimize the relapse rate.
Other Names:
  • Smoking cessation program
  • Body weight control
Behavioral: Self-management
The skills of body weight self-management (with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week)are delivered through individualized counseling and educational materials. Both the smoking cessation group and self-management group are provided with individualized counseling and incentives to help reach the goals of at least a 7 percent weight loss.
Other Names:
  • lifestyle change
  • body weight control
  • diet modifications
  • exercise
Active Comparator: Self-management
Participants who decide not to attend the smoking cessation program will be classified as self-management group. They are still provided with standardized diet and lifestyle education, with prospective follow-up of Fagerström Test for Nicotine Dependence (FTND) scores, breath carbon monoxide (CO) levels, anthropometric indices and blood tests every 3-6 months. The skills of body weight self-management (with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week) are delivered through individualized counseling and educational materials.
Behavioral: Self-management
The skills of body weight self-management (with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week)are delivered through individualized counseling and educational materials. Both the smoking cessation group and self-management group are provided with individualized counseling and incentives to help reach the goals of at least a 7 percent weight loss.
Other Names:
  • lifestyle change
  • body weight control
  • diet modifications
  • exercise

  Hide Detailed Description

Detailed Description:

The investigators plan to recruit the study participants from 1) individuals who had abnormal glucose data at employment health examination or adult preventive care service in about 20 communities, including Yunlin, Changhua, Chiayi, and Taipei; 2) patients who has past history of metabolic syndrome and has been regularly followed-up at National Taiwan University Hospital and its Yun-Lin branch. All participants should give informed consent for this project and medical record review, with personal data protected.

A history of diabetes, hypertension, FTND, alcohol consumption, physical activity, depression, sleep quality, and current medications is collected through standardized personal interview. Prediabetics are those repeatedly having either of the following: 1) plasma glucose 100 to 125 mg/dL (5.6 to 6.9 mmol/L) in the fasting state; 2) plasma glucose 140 to 199 mg/dL (7.8 to 11.0 mmol/L) two hours after a 75-g oral glucose load; 3) glycosylated hemoglobin (A1C) 5.7% to 6.4%, in the absence of diabetic medications. Prediabetics who smoke ≥10 CPD for at least 6 months are classified as prediabetic smokers. Prediabetic non-smokers are also recruited.

According an online sample size calculator (www.openepi.com), the investigators estimate to recruit at least 596 prediabetic smokers, in case 33% (199) of them joining the smoking cessation program, to reach a 90% power and two-sided confidence interval 95% for the detection of a 50% reduction from a risk for incident DM at 3-year follow-up.17 Besides, the investigators intend to recruit a total of 600 prediabetic non-smokers, including past smokers, for baseline analysis.

Body height and weight are measured using a single stadiometer, and body mass index (BMI) was calculated. The participants are classified as either normal or underweight (BMI <23 kg/m2), overweight (BMI 23 to 24.9 kg/m2), or obese (BMI ≥25 kg/m2), according to the World Health Organization criteria for Asian populations. Waist circumference is taken at the end of exhalation in the horizontal plane at the midway point between the inferior margin of the lowest rib and the iliac crest. Central obesity is defined as a waist circumference ≥90 cm for men or ≥80 cm for women, according to the criteria for metabolic syndrome used in Taiwan (www.hpa.gov.tw). Blood pressure (BP) is measured with an electronic sphygmomanometer with the patient seated after resting for at least ten minutes. Each participant undergoes laboratory testing after fasting for at least ten hours. Serological tests include serum hepatitis B surface antigen, serum antibody to hepatitis C virus, and hepatitis B e antigen, determined via a microparticle enzyme immunoassay (Abbott Laboratories, Illinois, USA). Hepatitis B viral load for hepatitis B carriers is measured with a COBAS TaqMan real-time polymerase chain reaction assay (Roche Diagnostics, Basel, Switzerland), detecting an upper limit of 640,200,000 copies/mL and a lower limit of 35 copies/mL (1 copies/mL = 0.1718 IU/mL). Serum adiponectin levels (in μg/mL) are determined by using the Procarta Cytokine Assay Kit (Affymetrix, Inc., California, USA) as in our recent report.

Plasma glucose levels are determined through the hexokinase method (1 mg/dL = 0.0555 mmol/L). Serum fasting insulin levels are measured using the COBAS electrochemiluminescence immunoassay (Roche Diagnostics, Basel, Switzerland) (1 μIU/mL = 6.945 pmol/L). Insulin resistance scores are determined by the homeostasis model assessment of insulin resistance (HOMA-IR),23 as calculated by the following formula: HOMA-IR score = fasting insulin (μIU/mL) × fasting glucose (mg/dL)/405. Participants will be categorized as insulin resistant if the HOMA-IR is 2.5 or higher. Plasma lipid, alanine aminotransferase (ALT), and creatinine levels are measured using a Hitachi 7150 Automated analyzer (Hitachi, Tokyo, Japan). Estimated glomerular filtration rate (eGFR) is calculated using the four-variable version of the Modification of Diet in Renal Disease Study equation for Chinese Patients.25 Briefly, eGFR (ml/min per 1.73 m2) = 175 × (serum creatinine -1.234) × (age -0.179) × 0.79 (if female). The hypertriglyceridemia is defined as a plasma triglycerides level ≥150 mg/dL (1.70 mmol/L); and the hypercholesterolemia is defined as a plasma total cholesterol level ≥200 mg/dL (5.18 mmol/L). The low high-density lipoprotein cholesterol (HDL-C) is defined as a serum HDL level <40 mg/dL (1.04 mmol/L) in men and <50 mg/dL (1.29 mmol/L) in women.

Metabolic syndrome is defined clinically, based on the presence of three or more of the American Heart Association/National Heart Lung Blood Institute (AHA/NHLBI) criteria: (i) central obesity; (ii) hypertriglyceridemia or on drugs for elevated triglycerides; (iii) a low HDL-C level or on drugs for reduced HDL-C; (iv) high BP (≥130/85 mm Hg) or on antihypertensive drugs; and (v) a high fasting plasma glucose or taking anti-diabetic drugs for hyperglycemia. The International Diabetes Federation (IDF) criteria are also applied when defining metabolic syndrome, if participants have central obesity plus any two of the other four components.

For descriptive analyses, values are presented as either a number (percent) or mean ± standard deviation (SD). For univariate analyses, categorical data are compared by means of the χ2 test or Fisher exact test. Continuous variables are compared using the two-sample Student's t-test. Statistical significance levels are determined by two-tailed tests (P value < 0.05). In the end of enrollment (July of 2015), we will compare baseline characteristics among prediabetic smokers and prediabetic non-smokers, stratified by gender and BMI groups. Subgroup analysis will explore the association between adipocytokines, BMI, metabolic factors and viral load for prediabetic hepatitis B carriers.

Changes in smoking habit for prediabetic smokers are recorded every 3 to 6 months. In the end of follow-up, hazard ratios (HRs) and 95% confidence intervals (95% CIs) of smoking cessation for incident DM risk or other outcome parameters during a 3 to 5-year follow-up period are estimated by multivariate Cox regression models after controlling age, gender, BMI (time-varying covariate) or body weight change (gainer, reducer, maintainer), BP, lipids, current medications, plasma ALT level, eGFR, daily coffee consumption, alcohol consumption, physical activity, depression, and sleep quality. Both intention-to-treat analysis and per-protocol analysis will be performed (Figure 1a, 1b). The former is based on the initial group assignment and not on the treatment eventually received. In the latter analysis, only participants who complete the entire clinical trial according to the protocol are counted towards the final results. That is, the independent variable "smoking cessation" reserves only for prediabetic smokers who succeed in quitting and keeping no relapse. For those who fail in quitting or keeping no relapse, they are still classified as self-management group and the individual follow-up period is from the study enrollment.

We assume missing values over time as missing at random and do listwise deletion. We will test the assumption of proportional hazards by Kaplan-Meier curves for time fixed covariates, and by creating selected time dependent variables inside PROC PHREG with PROPORTIONALITY_TEST statement. Stratification analysis by baseline BMI group may be done. Additive and multiplicative interaction between change in smoking status and body weight on DM risk will also be estimated. Subgroup follow-up analysis will explore the association between change in adipocytokines, BMI, metabolic factors and viral load in prediabetic hepatitis B carriers. Unadjusted Kaplan-Meier survival curves of liver cancer for quitters versus non-quitters will be drawn. All of the abovementioned statistical analyses are performed with SAS software version 9.3 (SAS Institute Inc., Cary, NC, USA).

  Eligibility

Ages Eligible for Study:   30 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Individuals aged from 30 to 75 years
  • Prediabetics (ADA criteria): including prediabetic smokers and non-smokers

Exclusion Criteria:

  • Acute cardiac conditions within 3months
  • Acute renal failure
  • Chronic glomerulonephritis
  • Polycystic kidney disease
  • Use of diabetic medications, steroids, lithium or antipsychotics
  • Pregnancy or breast-feeding
  • Malignancy.
  • The elderly adults visiting two or more hospitals due to multiple diseases
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01926041

Contacts
Contact: Chien-Hsieh Chiang, MD, MPH +886-920511256 jiansie@ntu.edu.tw

Locations
Taiwan
National Taiwan University Hospital Yun-Lin branch Recruiting
Yunlin, Taiwan, 640
Contact: Chien-Hsieh Chiang, MD, MPH    +886-9-20511256    jiansie@ntu.edu.tw   
Contact: Kuo-Chin Huang, MD, PhD         
Principal Investigator: Chien-Hsieh Chiang, MD, MPH         
Sub-Investigator: Kuo-Chin Huang, MD, PhD         
Sponsors and Collaborators
National Taiwan University Hospital
National Science Council, Taiwan
Investigators
Principal Investigator: Chien-Hsieh Chiang, MD, MPH National Taiwan Univeristy Hospital Yun-Lin Branch & College of Medicine
  More Information

Additional Information:
Publications:

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT01926041     History of Changes
Other Study ID Numbers: 201303041RINB
Study First Received: August 6, 2013
Last Updated: April 13, 2014
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
community
preventive medicine
prediabetes
smoking cessation

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Intolerance
Prediabetic State
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperglycemia

ClinicalTrials.gov processed this record on August 18, 2014