The Effectiveness of Smoking Cessation in Prediabetic Smokers

Diabetes Mellitus Clinical Trial

Official title:

The Effectiveness of Smoking Cessation in Prediabetic Smokers

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01926041
• Other study ID #: 201303041RINB
• Status: Active, not recruiting
• Phase: N/A
• Start date: August 1, 2013
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Existing literature investigating the impact of smoking cessation on new-onset diabetes mellitus (DM) risk is conflicting.

Combing the need for smoking cessation and body weight self-management to prevent the progression of prediabetes stage into DM, with the public implementation of the second-generation cessation program, we aimed to study the effectiveness of the Fight Tobacco and Stay Fit (FIT2) program aiming at promoting smoking cessation and restricting post-cessation weight gain (PCWG) together in prediabetic smokers regarding long-term glycemic and DM-related health outcomes.

Description:

Participants:

We expect to recruit study participants at National Taiwan University Hospital and its Yunlin branch, where a systematic identification system has been applied to classify the tobacco addiction status of every patient in outpatient clinics. This study invites identified current smokers to undergo screening tests between August 2013 to January 2017. All participants should give informed consent, with personal data protected. Only individuals aged 30 to 75 years are included. A history of diabetes, hypertension, Fagerström test for nicotine dependence, alcohol consumption, physical activity, depression, sleep quality, and current medications is collected through standardized personal interviews. Prediabetic participants are those who repeatedly have 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. Prediabetic participants who smoke ≥10 CPD for at least 6 months are classified as prediabetic smokers. Excluded are those with existing diagnosis of DM, thyroid diseases, acute cardiac conditions within 3 months, acute renal failure, chronic glomerulonephritis, polycystic kidney disease, mental health disorders ever diagnosed by psychiatrists, pregnancy, breast-feeding, malignancy; or current use of diabetic medications, smoking cessation medications, steroids, lithium or antipsychotics. Information about tobacco use, alcohol consumption, physical activity, depression, sleep quality, personal medical histories, and current medications is collected through standardized personal interviews and medical records. The study protocol was approved by the National Taiwan University Hospital Research Ethics Committee.

Sample size estimation We estimate to recruit at least 596 prediabetic smokers, 33% (199) of whom decide to join the intervention, to reach 90% power and a two-sided 95% CI for the detection of a 50% risk reduction, assuming 30% as the risk of incident T2D during follow-up in the usual care group.

Assignment, prospective follow-up, and analytic design The assignment of this trial is based on shared decision-making. At baseline, all eligible prediabetic smokers are asked if they would like to join the Fight Tobacco and Stay Fit (FIT2) program or just receive usual care. Beginning at enrollment, the smoking status, breath carbon monoxide levels, anthropometric indices, automated office and home blood pressures, and blood tests were recorded every six months. The intention-to-treat analysis is performed among all participants joining the FIT2 program and receiving usual care. The modified per-protocol analysis is adopted to compare participants with documented abstinence at prespecified study ends (e.g., 10 years) with the controls.

The FIT2 program and post-program abstinence:

The FIT2 program is a 16-week smoking cessation program that combines varenicline prescription with individualized counseling on not only smoking cessation but also weight control techniques. Participants in this group can receive their medications for up to 16 weeks within one year. Each participant also received counseling for individualized techniques for smoking cessation and body weight control at each visit. We do not prescribe nicotine replacement therapy (NRT) because it may induce insulin resistance and confound our study outcome. Bupropion is not available for smoking cessation in our institutions. Varenicline users are encouraged either to set their quit day 8 days after starting the medication; 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). Varenicline users are also forbidden to use NRT during the study period. The varenicline prescription adheres to regulations by the Health Promotion Administration, Ministry of Health and Welfare, Taiwan (www.hpa.gov.tw) and manufacturer's directions, usually initiated at 0.5 mg once daily for the first three days and then increased to 1 mg once daily. From day 8 to up to 16 weeks, the recommended dose is 1 mg varenicline twice daily. 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.

Smoking status is assessed by self-reported 7-day point-prevalence abstinence, confirmed by a breath CO level. 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. We provide participants in the intervention group with individualized counseling to help minimize the relapse rate.

In addition to varenicline prescription and smoking cessation counseling covered in conventional smoking cessation services, the FIT2 program also offers individualized weekly behavior coaching in diet and physical activity to restrict PCWG. The FIT2 participants are encouraged to do at least 150 minutes of moderate-intensity (3.0-6.0 metabolic equivalents) aerobic physical activity throughout the week. The counseling sessions allow opportunities to identify obstacles to lifestyle change and to discuss approaches with a professional panel of dietitians and certified personal trainers. The FIT2 participants are encouraged to do at least 150 minutes of moderate-intensity (3.0-6.0 metabolic equivalents) aerobic physical activity throughout the week. Emphasis is placed on checking the weekly diary for body weight, food, and physical activity through protected cellphone messages between participants and the assigned panel professionals. For those who gain weight, more intensive ways of calorie restriction and physical activity (at least 300 minutes of moderate-intensity aerobic physical activity per week) are instructed.

Post-program smoking status is recorded weekly from 16 weeks to six months by self-reported 7-day point prevalence of abstinence and a breath carbon monoxide level of <6 ppm. Post-program quitters are those who quit successfully at 16 weeks after the FIT2 program and maintain their non-smoking status until the prespecified study ends (e.g., post-program abstinence at 10 years). For the modified per-protocol analysis, participants who fail to keep quit after the FIT2 program are reassigned to the control group.

Usual care and control:

Usual care is provided for prediabetic smokers who decide not to receive the FIT2 program. Usual care comprises encouragement to quit smoking and initiate a therapeutic lifestyle change at each visit. In the modified per-protocol analysis, the control group contains participants joining the FIT2 program who fail to achieve post-program abstinence and all participants receiving usual care, including those who quit smoking on their own.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 589
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

Inclusion Criteria:

• Individuals aged 30 to 75 years

• Prediabetic smokers

Exclusion Criteria

• existing diagnosis of DM or current use of diabetic medications

• thyroid diseases

• acute cardiac conditions within 3 months

• acute renal failure, chronic glomerulonephritis, or polycystic kidney disease

• mental health disorders ever diagnosed by psychiatrists

• pregnancy or breast-feeding

• malignancy

• current use of smoking cessation medications, steroids, lithium, or antipsychotics.

Related Conditions & MeSH terms

• Cigarette Smoking
• Diabetes Mellitus
• Glucose Intolerance
• Prediabetes
• Prediabetic State

Intervention

Drug:
• Varenicline for tobacco smoking cessation
The 16-week varenicline course conforms to real-practice government regulations in Taiwan.

Behavioral:
• Individualized counseling about both smoking cessation and weight control techniques
The FIT2 program also offers behavior coaching in diet and physical activity to restrict post-cessation weight gain, which is not covered in conventional smoking cessation services.

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hospital and its Yunlin branch	Taipei	Department Of Family Medicine

Sponsors (2)

Lead Sponsor	Collaborator
National Taiwan University Hospital	Ministry of Science and Technology, Taiwan

Country where clinical trial is conducted

Taiwan, 

References & Publications (12)

Bergman BC, Perreault L, Hunerdosse D, Kerege A, Playdon M, Samek AM, Eckel RH. Novel and reversible mechanisms of smoking-induced insulin resistance in humans. Diabetes. 2012 Dec;61(12):3156-66. doi: 10.2337/db12-0418. Epub 2012 Sep 10. — View Citation

Chang PH, Chiang CH, Ho WC, Wu PZ, Tsai JS, Guo FR. Combination therapy of varenicline with nicotine replacement therapy is better than varenicline alone: a systematic review and meta-analysis of randomized controlled trials. BMC Public Health. 2015 Jul 22;15:689. doi: 10.1186/s12889-015-2055-0. — View Citation

Chiang CH, Huang KC. Association between metabolic factors and chronic hepatitis B virus infection. World J Gastroenterol. 2014 Jun 21;20(23):7213-6. doi: 10.3748/wjg.v20.i23.7213. — View Citation

Chiang CH, Huang KC. Reply: To PMID 24425422. Hepatology. 2015 May;61(5):1763-4. doi: 10.1002/hep.27427. Epub 2015 Mar 23. No abstract available. — View Citation

Chiang CH, Lai JS, Hung SH, Lee LT, Sheu JC, Huang KC. Serum adiponectin levels are associated with hepatitis B viral load in overweight to obese hepatitis B virus carriers. Obesity (Silver Spring). 2013 Feb;21(2):291-6. doi: 10.1002/oby.20000. — View Citation

Chiang CH, Lee LT, Hung SH, Lin WY, Hung HF, Yang WS, Sung PK, Huang KC. Opposite association between diabetes, dyslipidemia, and hepatocellular carcinoma mortality in the middle-aged and elderly. Hepatology. 2014 Jun;59(6):2207-15. doi: 10.1002/hep.27014. Epub 2014 Apr 3. — View Citation

Chiang CH, Lu CW, Han HC, Hung SH, Lee YH, Yang KC, Huang KC. The Relationship of Diabetes and Smoking Status to Hepatocellular Carcinoma Mortality. Medicine (Baltimore). 2016 Feb;95(6):e2699. doi: 10.1097/MD.0000000000002699. — View Citation

Chiang CH, Yang HI, Jen CL, Lu SN, Wang LY, You SL, Su J, Iloeje UH, Chen CJ; REVEAL-HBV Study Group. Association between obesity, hypertriglyceridemia and low hepatitis B viral load. Int J Obes (Lond). 2013 Mar;37(3):410-5. doi: 10.1038/ijo.2012.63. Epub 2012 Apr 24. — View Citation

Clair C, Rigotti NA, Porneala B, Fox CS, D'Agostino RB, Pencina MJ, Meigs JB. Association of smoking cessation and weight change with cardiovascular disease among adults with and without diabetes. JAMA. 2013 Mar 13;309(10):1014-21. doi: 10.1001/jama.2013.1644. — View Citation

Cropsey KL, Eldridge GD, Weaver MF, Villalobos GC, Stitzer ML. Expired carbon monoxide levels in self-reported smokers and nonsmokers in prison. Nicotine Tob Res. 2006 Oct;8(5):653-9. doi: 10.1080/14622200600789684. — View Citation

Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO. The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict. 1991 Sep;86(9):1119-27. doi: 10.1111/j.1360-0443.1991.tb01879.x. — View Citation

Rennard S, Hughes J, Cinciripini PM, Kralikova E, Raupach T, Arteaga C, St Aubin LB, Russ C; Flexible Quit Date Study Group. A randomized placebo-controlled trial of varenicline for smoking cessation allowing flexible quit dates. Nicotine Tob Res. 2012 Mar;14(3):343-50. doi: 10.1093/ntr/ntr220. Epub 2011 Nov 11. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	10-year Type 2 DM Risk	This outcome will be collected between 2022 and 2026.	At 10 years
Other	10-year Probability of Regression to Normoglycemia	This outcome will be collected between 2022 and 2026.	At 10 years
Primary	Number of Participants With New-onset Type 2 Diabetes Mellitus (DM)	The primary outcome is type 2 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 type 2 DM.	Up to 5 years
Secondary	Number of Participants With Regression to Normoglycemia	Participants who regress to normoglycemia should met all the following conditions for more than six months and maintained such status until the study end: 1) plasma glucose <5.6 mmol/L (100 mg/dL) in the fasting state; 2) plasma glucose <7.8 mmol/L (140 mg/dL) two hours after a 75-g oral glucose load; or 3) HbA1c<39 mmol/mol (5.7%), in the absence of antidiabetic drugs.	Up to 5 years
Secondary	Major Adverse Cardiac Events	Cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke diagnosed by specialists according to medical records	At 10 years (between 2022 and 2026)
Secondary	Chronic Kidney Disease Progression	Each participant is evaluated for the renal outcome every six months and at 10 years. Defined as progression to macroalbuminuria [urinary albumin-to-creatinine ratio (UACR), >300 mg of albumin per gram of creatinine] for = 3 months, or decrease in estimated glomerular filtration rate (eGFR) to <60mL/min/1.73 m2 for = 3 months, as calculated by the four-variable Modification of Diet in Renal Disease (MDRD) formula, and incident albuminuria for = 3 months.	Every 6 months and at 10 years (between 2022 and 2026)
Secondary	NAFLD Progression	Each participant is evaluated for the steatohepatitic outcome using FIB-4 scores, BARD scores, liver stiffness measurement (LSM) every six months and at 10 years. A FIB-4 score <1.45 means a low risk of advanced fibrosis, whereas patients with a score >3.25 are likely to have advanced fibrosis. A BARD score of 2-4 was associated with an OR for advanced fibrosis of 17 (CI 9.2-31.9) and a negative predictive value of 96%. LSM is useful to exclude advanced NASH fibrosis with a high negative predictive value (at a cutoff <7 kPa).; Ref: FIB-4 scores (www.mdcalc.com/fibrosis-4-fib-4-index-liver-fibrosis); BARD scores (www.mdcalc.com/bard-score-nafld-fibrosis);	Every 6 months and at 10 years (between 2022 and 2026)
Secondary	Malignancy Incidence	Incident malignancies based on medical records are accessed at 10 years, confirmed by national cancer registry system.	At 10 years (between 2022 and 2026)
Secondary	All-Cause Mortality	Deaths are ascertained at 10 years by computer linkage to the national death registry (death certificates were created by the Ministry of Health and Welfare, Taiwan) using ID numbers and these death certificates have been validated.	At 10 years (between 2022 and 2026)
Secondary	HbA1c Change Between Baseline and 6 Months	The HbA1c change (in percentage of HbA1c) was calculated from values between baseline and 6 months.	Baseline and 6 months