Assessing Progression to Type-2 Diabetes (APT-2D): A Prospective Cohort Study Expanded From BRITE-SPOT (Bio-bank and Registry for StratIfication and Targeted intErventions in the Spectrum Of Type 2 Diabetes)

Diabetes Clinical Trial

— APT-2D  

Official title:

Assessing Progression to Type-2 Diabetes (APT-2D): A Prospective Cohort Study Expanded From BRITE-SPOT (Bio-bank and Registry for StratIfication and Targeted intErventions in the Spectrum Of Type 2 Diabetes)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02838693
• Other study ID #: 28431754DIA4019
• Status: Recruiting
• Phase: N/A
• First received: June 21, 2016
• Last updated: July 21, 2016
• Start date: March 2016
• Est. completion date: December 2021

Study information

• Verified date: July 2016
• Source: National University Hospital, Singapore
• Contact: Sue-Anne Toh, MBBChir, MSc, MA
• Phone: +65 67722195
• Email: mdcsates[@]nus.edu.sg
• Is FDA regulated: No
• Health authority: Singapore: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

The Bio-bank and Registry for StratIfication and Targeted intErventions in the Spectrum Of Type 2 Diabetes (BRITE-SPOT) has been set up to prospectively collect clinical data and biologically relevant samples from individuals with, and at risk for type 2 diabetes (T2D), with the aim of delineating factors related to susceptibility, progression, complications and response to treatment. Expanded from BRITE-SPOT, Assessing the Progression to Type - 2 Diabetes (APT-2D) is a prospective cohort with a focus on non-diabetics (normoglycemic or prediabetic), to expand the sample size and depth of metabolic phenotyping in these upstream groups, with the more targeted aim of delineating factors related to insulin sensitivity versus secretion, that relate to progression to T2D.

Description:

This is a prospective open cohort study.

The study will comprise the following periods:

Screening

• Complete screening checklist and informed consent form

Procedures.

• Following the screening visit, subjects are required to return to undergo the following:

• Oral Glucose Tolerance Test (OGTT) to assess glucose tolerance and beta cell function

• Frequently-Sampled Intravenous Glucose Tolerance test (FSIVGTT) to assess acute insulin response to glucose

• Euglycemic Hyperinsulinemic Clamp (EHC) to obtain the insulin sensitivity index and assess insulin action

• The Disposition index (DI) that quantifies the relationship between insulin sensitivity and insulin secretion, will be determined through the results obtained during FSIVGTT and EHC to determine subject's risk for Type 2 diabetes.

• OGTT will be repeated every 6 months to assess for conversion to Type 2 Diabetes. Plasma C-peptide, and glucose will be measured at 7 time points during the OGTT for minimal model assessment of beta cell function

• FSIVGTT and EHC will be repeated within 3 months of conversion to Type 2 Diabetes, or at 3 years from recruitment, whichever comes sooner.

Normoglycemic Subjects: 800 Pre-Diabetic Subjects: 1500

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2300
• Est. completion date: December 2021
• Est. primary completion date: September 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Ability to give informed consent

2. At least 30 years old, and not older than 65 years

3. Overtly healthy males or females, as determined by medical history, physical examination and laboratory results

4. Not on any regular medications. Subjects using traditional medicine concomitantly will also be excluded in this study

Exclusion Criteria:

1. History or presence of current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, malignancy or neurological disorders capable of significantly altering the performance of the biomarker panel; or of interfering with the interpretation of data

2. Known or ongoing psychiatric disorders within 3 years

3. Regularly use known drugs of abuse within 3 years

4. Women who are pregnant or lactating

5. Have donated blood of more than 500 mL within 4 weeks of study enrollment.

6. Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)

7. Uncontrolled hypertension (blood pressure [BP] >160/100mmHg

8. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1

9. Treatment with any investigational drug, or biological agent within one (1) month of screening or plans to enter into an investigational drug/ biological agent study during the duration of this study

10. Known allergy to insulin

11. History of bleeding diathesis or coagulopathy

12. Any of the following laboratory values at screening:

• LDL > 190mg/dL (>4.9mmol/L)

• TG > 500mg/dL (>5.6mmol/L)

• Hba1C >= 6.5%

• Fasting glucose >=126mg/dL(>=7mmol/L) or 2 hour post-prandial glucose >=200mg/dL (>=11.1mmol/L)

• ALT > 3.0 x upper limit of normal

• Estimated creatinine clearance <60 mL/min

13. Have any other conditions, which, in the opinion of the Investigator would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the study

14. Significant change in weight (+/- 5%) during the past month

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Glucose Intolerance
• Pre-diabetes
• Prediabetic State

Intervention

Procedure:
• Not applicable. This is an observational study.
Not applicable. This is an observational study.

Locations

Country	Name	City	State
Singapore	National University Hospital	Singapore

Sponsors (3)

Lead Sponsor	Collaborator
Medicine	Janssen Pharmaceuticals, National Medical Research Council (NMRC), Singapore

Country where clinical trial is conducted

Singapore, 

References & Publications (19)

Bagust A, Beale S. Deteriorating beta-cell function in type 2 diabetes: a long-term model. QJM. 2003 Apr;96(4):281-8. — View Citation

Bergman RN, Phillips LS, Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest. 1981 Dec;68(6):1456-67. — View Citation

Chen M, Porte D Jr. The effect of rate and dose of glucose infusion on the acute insulin response in man. J Clin Endocrinol Metab. 1976 Jun;42(6):1168-75. — View Citation

Cook MN, Girman CJ, Stein PP, Alexander CM, Holman RR. Glycemic control continues to deteriorate after sulfonylureas are added to metformin among patients with type 2 diabetes. Diabetes Care. 2005 May;28(5):995-1000. — View Citation

Dalla Man C, Campioni M, Polonsky KS, Basu R, Rizza RA, Toffolo G, Cobelli C. Two-hour seven-sample oral glucose tolerance test and meal protocol: minimal model assessment of beta-cell responsivity and insulin sensitivity in nondiabetic individuals. Diabetes. 2005 Nov;54(11):3265-73. — View Citation

Donnan PT, MacDonald TM, Morris AD. Adherence to prescribed oral hypoglycaemic medication in a population of patients with Type 2 diabetes: a retrospective cohort study. Diabet Med. 2002 Apr;19(4):279-84. — View Citation

Jin W, Patti ME. Genetic determinants and molecular pathways in the pathogenesis of Type 2 diabetes. Clin Sci (Lond). 2009 Jan;116(2):99-111. doi: 10.1042/CS20080090. Review. — View Citation

Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW, Neifing JL, Ward WK, Beard JC, Palmer JP, et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes. 1993 Nov;42(11):1663-72. — View Citation

Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov. 2004 Aug;3(8):711-5. — View Citation

Levy J, Atkinson AB, Bell PM, McCance DR, Hadden DR. Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study. Diabet Med. 1998 Apr;15(4):290-6. — View Citation

Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC. UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group. Diabet Med. 1998 Apr;15(4):297-303. — View Citation

Paul SM, Mytelka DS, Dunwiddie CT, Persinger CC, Munos BH, Lindborg SR, Schacht AL. How to improve R&D productivity: the pharmaceutical industry's grand challenge. Nat Rev Drug Discov. 2010 Mar;9(3):203-14. doi: 10.1038/nrd3078. Epub 2010 Feb 19. — View Citation

Riese DJ 2nd, Settleman J, Neary K, DiMaio D. Bovine papillomavirus E2 repressor mutant displays a high-copy-number phenotype and enhanced transforming activity. J Virol. 1990 Feb;64(2):944-9. — View Citation

Ringborg A, Lindgren P, Yin DD, Martinell M, Stålhammar J. Time to insulin treatment and factors associated with insulin prescription in Swedish patients with type 2 diabetes. Diabetes Metab. 2010 Jun;36(3):198-203. doi: 10.1016/j.diabet.2009.11.006. Epub 2010 Mar 28. — View Citation

Tai ES, Goh SY, Lee JJ, Wong MS, Heng D, Hughes K, Chew SK, Cutter J, Chew W, Gu K, Chia KS, Tan CE. Lowering the criterion for impaired fasting glucose: impact on disease prevalence and associated risk of diabetes and ischemic heart disease. Diabetes Care. 2004 Jul;27(7):1728-34. — View Citation

Tan CE, Emmanuel SC, Tan BY, Jacob E. Prevalence of diabetes and ethnic differences in cardiovascular risk factors. The 1992 Singapore National Health Survey. Diabetes Care. 1999 Feb;22(2):241-7. — View Citation

Turner R, Stratton I, Horton V, Manley S, Zimmet P, Mackay IR, Shattock M, Bottazzo GF, Holman R. UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet. 1997 Nov 1;350(9087):1288-93. Erratum in: Lancet 1998 Jan 31;351(9099):376. — View Citation

Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004 May;27(5):1047-53. — View Citation

Zhou K, Donnelly LA, Morris AD, Franks PW, Jennison C, Palmer CN, Pearson ER. Clinical and genetic determinants of progression of type 2 diabetes: a DIRECT study. Diabetes Care. 2014;37(3):718-24. doi: 10.2337/dc13-1995. Epub 2013 Nov 1. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in beta-cell function in Asian populations with normal glucose tolerance and prediabetes over 3 years.	Glucose & c-peptide laboratory results, from OGTT, will be used to assess glucose tolerance and beta cell function	Data for each participant will be analysed upon completion all their OGTT visits	No
Primary	Changes in insulin sensitivity in Asian populations with normal glucose tolerance and prediabetes over 3 years. Data will be presented at the end of 5.5years.	Disposition index assessed via glucose and insulin results from FSIVGTT and EHC.	Data for each participant will be analysed upon completion of both of the FSIVGTT and EHC visits	No
Secondary	To discover and/or validate biomarkers that predict which subjects will progress from NGT to prediabetes and/or from prediabetes to diabetes. Data will be presented at the end of 5.5years.	Biomarker panel will be conducted through testing of plasma and serum samples.	All samples collected during the study will be consolidated at the end of 5.5years or upon study completion, whichever that comes first, and analysed in one single batch to ensure consistency of the data	No