The Effectiveness of Smoking Cessation Clinics Combined With Coach-assisted Lifestyle Change in Prediabetic Smokers
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|ClinicalTrials.gov Identifier: NCT01926041|
Recruitment Status : Recruiting
First Posted : August 20, 2013
Last Update Posted : January 28, 2016
|First Submitted Date ICMJE||August 6, 2013|
|First Posted Date ICMJE||August 20, 2013|
|Last Update Posted Date||January 28, 2016|
|Study Start Date ICMJE||August 2013|
|Estimated Primary Completion Date||July 2020 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Diagnosis of diabetes mellitus by ADA criteria [ Time Frame: at least 3 years (from Aug 1, 2013) ]
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.
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01926041 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE
||All-cause mortality [ Time Frame: at least 3 years (from Aug 1, 2013) ]
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.
|Original Other Outcome Measures ICMJE||Same as current|
|Brief Title ICMJE||The Effectiveness of Smoking Cessation Clinics Combined With Coach-assisted Lifestyle Change in Prediabetic Smokers|
|Official Title ICMJE||The Effectiveness of Smoking Cessation Clinics Combined With Coach-assisted Lifestyle Change in Prediabetic Smokers|
Diabetes mellitus (DM) has been established to contribute to cardiovascular comorbidities, malignancies and higher mortalities. The management of DM is not limited to aggressively controlling sugar levels after the diagnosis; instead, should be emphasized more on effective modification for prediabetics. Smoking cessation were also demonstrated to improve insulin resistance. Nowadays, the 2nd-generation cessation program in Taiwan brings higher accessibility. However, there is little evidence on the long-term health outcomes of combining smoking cessation and coach-assisted lifestyle change for the prediabetics in the community.
The present new project extends the original pilot project (NSC 102-2628-B-002-046-MY2 and MOST 104-2314-B-002 -072) from August of 2013. The investigators have been making efforts to promote this project by cooperating with primary care doctors of the community medical groups and corporate nurses. Over 446 prediabetic smokers will be enrolled by July of 2017. The invention includes smoking cessation clinics for up to 16 weeks (from January to December of 2017) and coach-assisted lifestyle change (from January of 2017 to July of 2020 and later) for every participant joining intervention. The lifestyle coaches will help the participants in intervention group reach the goal of at least a 7 percent weight loss within the first 6 months. All smokers with prediabetes in intervention and self-management group are provided with educational materials for lifestyle change. All prediabetic smokers are prospectively followed up every 6 months till July of 2020 and later for smoking status, anthropometric indices and blood tests.
Regarding the potential contribution to the national socio-economic development, this project will strengthen the motivation of smoking cessation in prediabetic smokers. Academically, cox regression will be used to investigate the effectiveness of the smoking cessation combined with coach-assisted lifestyle change on DM prevention in smokers with prediabetes. This prospective project will contribute to community-based diabetes research in preventive medicine.
The investigators plan to recruit the study participants from 1) individuals who had abnormal glucose data at employment health examination or community adult preventive care service in Yunlin 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. Only individuals aged from 30 to 75 years are included.
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 446 prediabetic smokers, in case 33% (149) of them joining the intervention program, to reach a 80% power and two-sided confidence interval 95% for the detection of a 50% risk reduction, assuming 30% as the risk of incident DM at 3-year follow-up in prediabetic smokers not joining the intervention program.
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 the investigators' 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.
After the baseline assessment, all prediabetic smokers are provided with educational materials for lifestyle changes. All prediabetic smokers are prospectively followed up every 6 months till July of 2020 and later for smoking status, FTND scores, breath carbon monoxide (CO) levels, anthropometric indices and blood tests. Prediabetic non-smokers are not followed in this study. At each visit, all prediabetic smokers will be asked if they want to join the intervention including both smoking cessation program and coach-assisted lifestyle change. Randomization is not ethically allowed in this study. Participants were encouraged to weigh themselves at home daily or a minimum of once per week.
Intervention group The invention includes smoking cessation clinics for up to 16 weeks (from January to December of 2017) and coach-assisted lifestyle change (from January of 2017 to July of 2020 and later) for every participant joining intervention. Participants who decide to join the intervention will be referred to smoking cessation clinics at National Taiwan University Hospital and its Yun-Lin branch (Table 1, Figure 1). Participants in this group can receive their medications up to 16 weeks within one year. Each participant in intervention group receives counseling for individualized smoking cessation techniques at each visit. In addition, each participant is assigned two lifestyle coaches giving weekly and standardized instruction in diet and physical activity to help reach the goals of at least a 7 percent weight loss within the first 6 months. Two lifestyle coaches (a dietitian and a physical therapist) is responsible for about 40 participants. Each coach of physical activity offers supervised physical activity sessions at least two times per week (perhaps through cell phone apps). All lifestyle coaches also contact the participants weekly which provided an opportunity to identify a variety of obstacles to lifestyle change for their participants and to discuss behavioral approaches to improve specific problems. If participants did not have a bathroom scale at home, they were given one. Emphasis was placed on using the scale as an important feedback and learning tool for how to better regulate personal diet and exercise behaviors.
The investigators do not prescribe the nicotine replacement therapy because it may induce insulin resistance and confound the study outcome. Bupropion is not available for smoking cessation in the study institutions. Varenicline users are encouraged either to set their quit day 8 days after starting the medication;30 or to freely choose quit day at any time between Days 8 and 35 after starting treatment (i.e., following drug titration that took place within the first week).31 Varenicline users are also forbidden to use the nicotine replacement therapy during the study period. Varenicline is administered according to the manufacturer's directions, and a 1- to 4-week supply of medicine is prescribed at every clinic visit. During the therapy course, physicians are allowed to adjust varenicline dosage according to tolerability. Drug adverse events, withdrawal symptoms, and perceived barriers to quitting should be recorded and addressed. Physicians should emphasize that if there are any uncontrolled depressed moods, suicidal thoughts, or attempts, they are to cease varenicline treatment and consult a psychiatrist immediately.
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.32 Cotinine is not used to assess abstinence because, when used with self-report to indicate whether a person has smoked, CO and cotinine levels show high agreement.14,33 A senior registered nurse provides every participant joining smoking cessation program with individualized counseling to help minimize the relapse rate.
Self-management group Participants who decide NOT to attend the intervention program are classified as self-management group. All smokers with prediabetes in intervention and self-management group are provided with educational materials for lifestyle change. They are still provided with educational materials of standardized diet and exercise. They are prospectively followed up every 6 months till July of 2020 and later for FTND scores, breath CO levels, anthropometric indices and blood tests (Table 1, Figure 1). 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)19 are delivered through educational materials.
Statistical analysis 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 2017), the investigators will compare baseline characteristics among prediabetic smokers and prediabetic non-smokers, stratified by gender and BMI groups.
Changes in smoking habit for prediabetic smokers are recorded every 6 months from July of 2017. In the end of follow-up, hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the intervention (both smoking cessation program and coach-assisted lifestyle change) for incident DM risk or other outcome parameters during 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. The per-protocol analysis will be performed (Figure 1). Only participants who complete the entire clinical trial according to the protocol are counted towards the final results. The independent variable "intervention" 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. The failure of reaching goals of body weight reduction or smoking cessation will NOT change the group assignment.
The investigators assume missing values over time as missing at random and do listwise deletion. The investigators 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. Unadjusted Kaplan-Meier survival curves of DM incidence for quitters versus non-quitters will be drawn. All of the abovementioned statistical analyses are performed with SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA).
|Study Type ICMJE||Interventional|
|Study Phase||Not Applicable|
|Study Design ICMJE||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Estimated Study Completion Date||July 2020|
|Estimated Primary Completion Date||July 2020 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||30 Years to 75 Years (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Listed Location Countries ICMJE||Taiwan|
|Removed Location Countries|
|NCT Number ICMJE||NCT01926041|
|Other Study ID Numbers ICMJE||201303041RINB|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Taiwan University Hospital|
|Study Sponsor ICMJE||National Taiwan University Hospital|
|Collaborators ICMJE||Ministry of Science and Technology, Taiwan|
|PRS Account||National Taiwan University Hospital|
|Verification Date||January 2016|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP