Genetic Testing and Counseling to Reduce Diabetic Complications

NCT02364323 | Completed

• 1 other identifier: GEM Study
• Study Type: interventional
• Target: 435
• Locations: 1 country
• Sites: 1

Brief Summary

The risk of diabetic kidney complications includes non-modifiable risk factors such as genetic predictors, as well as modifiable risk factors such as hyperglycaemia, hypertension, hyperlipidaemia and proteinuria. Genetic testing for personalized medicine is increasing in popularity, though evidence that genetic testing can empower patients to modify behaviour and reduce clinical risk remains lacking. In this project, the investigators aim to utilize a personalized risk counseling with genetic testing to evaluate its impact on risk factor control in diabetic patients. The investigators hypothesize that knowledge of genetic +/- clinical risk will empower patients and lead to improvement in the number of treatment targets achieved. The investigators will recruit 400 patients with diabetes. All subjects will undergo a comprehensive assessment of the risk of diabetic complications based on clinical risk factors. Half of the patients will be randomized to receive additional genetic testing of a panel of genetic markers proven to predict renal complications in our population: ACE I/D, aldose reductase (CA)n and PRKCB1 gene polymorphisms. The results of personalized risk assessment will be communicated by a health counsellor in the intervention arm. The impact of testing and patient knowledge of the result of genetic testing on achievement of treatment targets (A1c, BP, LDL-cholesterol, TG, use of ACEI/ARB) and patient behavior will be evaluated after 12 months. The other arm will receive results of the genetic testing at the completion of the study period. The study will help towards developing a strategy to empower patients through structured and personalized risk assessment will provide a novel approach to identify high-risk subjects for early intensive management, and may lead to reduction in long-term complications.

Conditions

Diabetic Complication

Outcome Measures

Primary Outcomes (1)

• percentage of patients attaining ≥ 3 pre-defined treatment targets from the following treatment targets: 1) BP <130/80 mm Hg 2) HbA1c <7% 3) Calculated LDL-cholesterol <2.6mmol/l 4) Fasting TG <2mmol/l 5) Use of ACEI or ARB

  primary outcome of 3 out of 5 targets achieved as defined above

  At 1 year

Secondary Outcomes (3)

• microalbuminuria as a marker of degree of renal damage

  At 1 year

• Patient empowerment as measured on the Chinese Diabetes Empowerment Scale (DES)

  At 1 year

• Patient behavior measured on the Summary of Diabetes Self-care Activities (SDSCA)

  At 1 year

Study Arms (2)

Personalized risk counselling

EXPERIMENTAL

Intervention includes risk counseling to patients with diabetes on future risk of diabetic complications based on an established genetic counseling framework for common polygenic disorders which will be delivered to patient in a counselling sesssion 6 weeks after genetic testing

Behavioral: Personalized Risk Counselling

Normal usual care

PLACEBO COMPARATOR

Intervention includes normal usual care. General education on diabetes and diabetic complications

Other: Normal usual care

Interventions

Personalized Risk Counselling BEHAVIORAL

Motivational message- towards lifestyle change, improved compliance and risk factors control Review overall control of clinical risk factors based on lab test results

Personalized risk counselling

Normal usual care OTHER

General education on diabetes and diabetic complications

Normal usual care

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults with type 2 diabetes aged 40-75 who can give informed consent
• Subjects with no known chronic kidney disease (CKD defined as eGFR\<60ml/min at baseline)
• Suboptimal glucose control with HbA1c ≥ 7.5%
• Known history of hypertension including elevated BP ≥140/90 on more than one occasion

You may not qualify if:

• Subjects with known coronary artery disease or coronary revascularisation
• Subjects with previous history of cerebrovascular accident
• Subjects with known proliferative retinopathy or previous laser treatment for diabetic retinopathy
• Subjects with life-threatening conditions including malignancy
• Subjects with known psychiatric conditions including depression
• Subjects with significant renal impairment (eGFR\<60ml/min at baseline) or non-diabetic renal disease (e.g. biopsy-proven glomerulonephritis or obstructive uropathy)
• Subjects with major physical disability

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Prince of Wales Hospital

Shatin, Hong Kong

Location

Related Publications (18)

• Yang W, Lu J, Weng J, Jia W, Ji L, Xiao J, Shan Z, Liu J, Tian H, Ji Q, Zhu D, Ge J, Lin L, Chen L, Guo X, Zhao Z, Li Q, Zhou Z, Shan G, He J; China National Diabetes and Metabolic Disorders Study Group. Prevalence of diabetes among men and women in China. N Engl J Med. 2010 Mar 25;362(12):1090-101. doi: 10.1056/NEJMoa0908292.

  PMID: 20335585 BACKGROUND

• Chan JC, So W, Ma RC, Tong PC, Wong R, Yang X. The Complexity of Vascular and Non-Vascular Complications of Diabetes: The Hong Kong Diabetes Registry. Curr Cardiovasc Risk Rep. 2011 Jun;5(3):230-239. doi: 10.1007/s12170-011-0172-6. Epub 2011 Apr 12.

  PMID: 21654912 BACKGROUND

• Yang XL, So WY, Kong AP, Clarke P, Ho CS, Lam CW, Ng MH, Lyu RR, Yin DD, Chow CC, Cockram CS, Tong PC, Chan JC. End-stage renal disease risk equations for Hong Kong Chinese patients with type 2 diabetes: Hong Kong Diabetes Registry. Diabetologia. 2006 Oct;49(10):2299-308. doi: 10.1007/s00125-006-0376-3. Epub 2006 Aug 30.

  PMID: 16944095 BACKGROUND

• Chan BS, Tsang MW, Lee VW, Lee KK. Cost of Type 2 Diabetes mellitus in Hong Kong Chinese. Int J Clin Pharmacol Ther. 2007 Aug;45(8):455-68. doi: 10.5414/cpp45455.

  PMID: 17725179 BACKGROUND

• Luk AO, So WY, Ma RC, Kong AP, Ozaki R, Ng VS, Yu LW, Lau WW, Yang X, Chow FC, Chan JC, Tong PC; Hong Kong Diabetes Registry. Metabolic syndrome predicts new onset of chronic kidney disease in 5,829 patients with type 2 diabetes: a 5-year prospective analysis of the Hong Kong Diabetes Registry. Diabetes Care. 2008 Dec;31(12):2357-61. doi: 10.2337/dc08-0971. Epub 2008 Oct 3.

  PMID: 18835954 BACKGROUND

• Chan J, So W, Ko G, Tong P, Yang X, Ma R, Kong A, Wong R, Le Coguiec F, Tamesis B, Wolthers T, Lyubomirsky G, Chow P. The Joint Asia Diabetes Evaluation (JADE) Program: a web-based program to translate evidence to clinical practice in Type 2 diabetes. Diabet Med. 2009 Jul;26(7):693-9. doi: 10.1111/j.1464-5491.2009.02751.x.

  PMID: 19573118 BACKGROUND

• Ko GT, So WY, Tong PC, Le Coguiec F, Kerr D, Lyubomirsky G, Tamesis B, Wolthers T, Nan J, Chan J. From design to implementation--the Joint Asia Diabetes Evaluation (JADE) program: a descriptive report of an electronic web-based diabetes management program. BMC Med Inform Decis Mak. 2010 May 13;10:26. doi: 10.1186/1472-6947-10-26.

  PMID: 20465815 BACKGROUND

• Chan JC, So WY, Yeung CY, Ko GT, Lau IT, Tsang MW, Lau KP, Siu SC, Li JK, Yeung VT, Leung WY, Tong PC; SURE Study Group. Effects of structured versus usual care on renal endpoint in type 2 diabetes: the SURE study: a randomized multicenter translational study. Diabetes Care. 2009 Jun;32(6):977-82. doi: 10.2337/dc08-1908.

  PMID: 19460913 BACKGROUND

• Malandrino N, Smith RJ. Personalized medicine in diabetes. Clin Chem. 2011 Feb;57(2):231-40. doi: 10.1373/clinchem.2010.156901. Epub 2010 Dec 2.

  PMID: 21127150 BACKGROUND

• Wang Y, Ng MC, So WY, Tong PC, Ma RC, Chow CC, Cockram CS, Chan JC. Prognostic effect of insertion/deletion polymorphism of the ace gene on renal and cardiovascular clinical outcomes in Chinese patients with type 2 diabetes. Diabetes Care. 2005 Feb;28(2):348-54. doi: 10.2337/diacare.28.2.348.

  PMID: 15677791 BACKGROUND

• Wang Y, Luk AO, Ma RC, So WY, Tam CH, Ng MC, Yang X, Lam V, Tong PC, Chan JC. Predictive role of multilocus genetic polymorphisms in cardiovascular disease and inflammation-related genes on chronic kidney disease in Type 2 diabetes--an 8-year prospective cohort analysis of 1163 patients. Nephrol Dial Transplant. 2012 Jan;27(1):190-6. doi: 10.1093/ndt/gfr343. Epub 2011 Jul 15.

  PMID: 21765051 BACKGROUND

• Ma RC, Tam CH, Wang Y, Luk AO, Hu C, Yang X, Lam V, Chan AW, Ho JS, Chow CC, Tong PC, Jia W, Ng MC, So WY, Chan JC. Genetic variants of the protein kinase C-beta 1 gene and development of end-stage renal disease in patients with type 2 diabetes. JAMA. 2010 Aug 25;304(8):881-9. doi: 10.1001/jama.2010.1191.

  PMID: 20736472 BACKGROUND

• So WY, Wang Y, Ng MC, Yang X, Ma RC, Lam V, Kong AP, Tong PC, Chan JC. Aldose reductase genotypes and cardiorenal complications: an 8-year prospective analysis of 1,074 type 2 diabetic patients. Diabetes Care. 2008 Nov;31(11):2148-53. doi: 10.2337/dc08-0712. Epub 2008 Aug 20.

  PMID: 18716049 BACKGROUND

• Janssens AC, Gwinn M, Bradley LA, Oostra BA, van Duijn CM, Khoury MJ. A critical appraisal of the scientific basis of commercial genomic profiles used to assess health risks and personalize health interventions. Am J Hum Genet. 2008 Mar;82(3):593-9. doi: 10.1016/j.ajhg.2007.12.020.

  PMID: 18319070 BACKGROUND

• Grant RW, Hivert M, Pandiscio JC, Florez JC, Nathan DM, Meigs JB. The clinical application of genetic testing in type 2 diabetes: a patient and physician survey. Diabetologia. 2009 Nov;52(11):2299-2305. doi: 10.1007/s00125-009-1512-7. Epub 2009 Sep 2.

  PMID: 19727660 BACKGROUND

• Chen S, Chiu H, Xu B, Ma Y, Jin T, Wu M, Conwell Y. Reliability and validity of the PHQ-9 for screening late-life depression in Chinese primary care. Int J Geriatr Psychiatry. 2010 Nov;25(11):1127-33. doi: 10.1002/gps.2442.

  PMID: 20029795 BACKGROUND

• Ting RZ, Nan H, Yu MW, Kong AP, Ma RC, Wong RY, Loo K, So WY, Chow CC, Ko GT, Wing YK, Chan JC. Diabetes-related distress and physical and psychological health in chinese type 2 diabetic patients. Diabetes Care. 2011 May;34(5):1094-6. doi: 10.2337/dc10-1612. Epub 2011 Mar 11.

  PMID: 21398526 BACKGROUND

• Shiu AT, Martin CR, Thompson DR, Wong RY. Psychometric properties of the Chinese version of the diabetes empowerment scale. Psychol Health Med. 2006 May;11(2):198-208. doi: 10.1080/13548500500286845.

  PMID: 17129908 BACKGROUND

MeSH Terms

Conditions

Diabetes Complications

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Ronald C Ma, MB BChir

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 10, 2015
• First Posted: February 18, 2015
• Study Start: February 17, 2015
• Primary Completion: April 18, 2017
• Study Completion: December 31, 2018
• Last Updated: March 21, 2022

Record last verified: 2022-03

Locations

HK (1)