Clinical trial NCT02838693: 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)
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)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pre-diabetes
Diabetes
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
Collaborators: name: Janssen Pharmaceuticals
name: National Medical Research Council (NMRC), Singapore
First posted: 2016-07-20
Enrollment: 2300
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Normoglycemic: 800 Pre-diabetics: 1,500

Brief 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.

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Changes in beta-cell function in Asian populations with normal glucose tolerance and prediabetes over 3 years.
timeFrame: Data for each participant will be analysed upon completion all their OGTT visits
measure: 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.
timeFrame: Data for each participant will be analysed upon completion of both of the FSIVGTT and EHC visits
Secondary outcomes:
measure: 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.
timeFrame: 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
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: mdcsates@nus.edu.sg
name: Sue-Anne Toh, MBBChir, MSc, MA
role: PRINCIPAL_INVESTIGATOR
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