Precision Medicine in Chinese Patients With Young Onset Diabetes

NCT04049149 | Unknown

• 1 other identifier: CRE-2019.080
• Study Type: interventional
• Target: 884
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with young onset diabetes (YOD) are one of the most challenging groups of patients due to their long disease duration, complex causes, delayed interventions, psychosocial stress, poor adherence and frequent default. The investigator's previous studies indicate that provision of biogenetic information improved satisfaction, reduced ambiguity and improved self-efficacy in patients with T2D. Provision of personalized information using the web-based Joint Asia Diabetes Evaluation (JADE) Technology with risk stratification and decision support empowers better self care and medical intervention with improved control of risk factors. To further improve the precision of diagnosis for individualizing care, the use of CP, GADA, genetic risk scores (GRS) or rare genetic variants of maturity onset of diabetes (MODY) can help doctors select the most appropriate therapy in a timely manner. While patients with low CP, GADA and high GRS will benefit from early insulin therapy, some MODY variants are associated with good response to insulin-releasing oral drugs (e.g. sulphonylurea) which may spare the use of insulin with reduced patient distress and over-insulinization. By contrast, patients with high CP often due to obesity-associated insulin resistance should undergo intensive lifestyle modification and use of drugs with weight-reducing or neutral effects to avoid weight gain due to excessive dose of insulin.

Conditions

Type 2 Diabetes

Keywords

Young-onset type 2 diabetes

Outcome Measures

Primary Outcomes (4)

• Prevalence of C-Peptide (CP) and Glutamic Acid Decarboxylase Antibody (GADA) in Chinese adult patients with T2D (Part 1 of study)

  Between 1995 to 2004, all patients in the HKDR had structured assessment with storage of blood samples (collected at registration) for future research purpose. We shall measure CP and GADA in 4000-5000 patients.

  through study completion, an average of 4 years

• The correlation of C-Peptide (CP) and Glutamic Acid Decarboxylase Antibody (GADA) on clinical outcomes (Part 1 of study)

  Between 1995 to 2004, all patients in the HKDR had structured assessment with storage of blood samples (collected at registration) for future research purpose.

  through study completion, an average of 4 years

• Incidence of young-onset type 2 diabetes and its genetic susceptibility (Part 2 of study)

  Between 1998 to 2013, subjects from the HKFDS and the community-based LKS cohort had storage of blood samples at registration.

  through study completion, an average of 4 years

• Incidence of any diabetes-related micro/macrovascular endpoints (Part 3 of study)

  Incident including cardiovascular disease (coronary heart disease, congestive heart failure, stroke, peripheral artery disease), chronic kidney disease, all-cause death and/or incident/progression/remission of albuminuria, estimated glomerular filtration rate, retinopathy, visual acuity and sensory neuropathy

  through study completion, an average of 4 year

Secondary Outcomes (20)

• The levels of CP and GADA and the number of genetic variants for disease prognositication and classification to guide precision medicine in YOD (Part 1 and 2 of study)

  through study completion, an average of 4 years

• The number of genetic variants for disease prognositication and classification to guide precision medicine in YOD (Part 1 and 2 of study)

  through study completion, an average of 4 years

• The number of novel targets and pathways for discovery of drug targets with companian diagnostics (Part 1 and 2 of study)

  through study completion, an average of 4 years

• The number of patients attaining ≥3 cardiometabolic risk factors (Part 3 of study)

  through study completion, an average of 4 years

• Incidence of severe hypoglycaemia (Part 3 of study)

  through study completion, an average of 4 year

Study Arms (2)

JADE-PRISM group

OTHER

Only applicable in part 3 which is a randomized controlled trial. Part 1 and part 2 are the prospective cohort studies.

Other: Biogenetic explanation and endocrinologist intensive managment

JADE group

OTHER

Only applicable in part 3 which is a randomized controlled trial. Part 1 and part 2 are the prospective cohort studies.

Other: Usual care management

Interventions

Biogenetic explanation and endocrinologist intensive managment OTHER

* JADE report and JADE APP * Biogenetic explanation * First-year intensive management by endocrinologists * Follow up by their usual care doctors for continue treatment regimen maintenance. * Yearly DM nurses follow up for blood taking and questionnaires

JADE-PRISM group

Usual care management OTHER

* JADE report and JADE APP * Attend their usual care clinic for ongoing treatment * Yearly DM nurses follow up for blood taking and questionnaires

JADE group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Part 1: Prospective cohort of Chinese with type 2 diabetes
• Between 1995 and December 2004, 10,129 patients were assessed using structured protocol to esetablish the HKDR and of them, we have measured GADA and CP in 1400 patients with YOD. In this study, we shall measure CP and GADA in 4000 subjects from the HKDR with available GWAS data irrespective of their age of diagnosis. These samples were linked to our various databases by a unique identification code which will enable us to track the clinical outcomes including development of complications.
• Part 2: Family-based cohort of first-degree relatives of diabetic probands
• We shall utilize the resource of the HKDFS and control subjects to discover novel genetic variants of YOD. Subjects will be selected based on their status with or without diabetes. In 2012-2013, we ascertained the glycemic status of 365 siblings in the HKDFS and 452 participants of the community-based LKS cohort (aged 18-55 years) without diabetes at baseline (1998-2002).
• In this cohort, 167 participants (53.7%) with a family history of YOD, 68 participants (30.1%) with a family history of late onset diabetes and 40 (14.4%) participants without family history of diabetes developed diabetes. Amongst the 313 siblings with family history of YOD, 167 had diabetes at baseline or developed diabetes during follow up and 146 did not develop diabetes after 13 years giving 100-120 sibpairs for linkage analysis. These sequence data will be imputed with 500 YOD patients and 500 control subjects with exome data as well as 6000 patients in the HKDR with GWAS data for analysis for validation purpose.
• Part 3: RCT (PRISM)
• Non-type 1 diabetes (T1D)
• Chinese ethnicity
• Age between 18-50 years inclusive
• Age at diabetes diagnosis 40 years
• Able to understand study requirements and voluntarily agree to participate by providing written informed consent

You may not qualify if:

• Part 1/2:
• Subjects in the HKDR, HKFDS and LKS cohorts without or insuffiicent amount of biosamples for assays or sequencing.
• Part 3:
• T1D, defined by presentation with diabetic ketoacidosis or insulin requirement within 6 months of diagnosis.
• Reduced life expectancy due to terminal illness or otherwise deemed not appropriate per discretion of the investigator

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

The Chinese University of Hong Kong

Shatin, Hong Kong

Location

Related Publications (1)

• O CK, Fan YN, Fan B, Lim C, Lau ESH, Tsoi STF, Wan R, Lai WY, Poon EW, Ho J, Ho CCY, Fung C, Lee EK, Wong SY, Wang M, Ozaki R, Cheung E, Ma RCW, Chow E, Kong APS, Luk A, Chan JCN. Precision Medicine to Redefine Insulin Secretion and Monogenic Diabetes-Randomized Controlled Trial (PRISM-RCT) in Chinese patients with young-onset diabetes: design, methods and baseline characteristics. BMJ Open Diabetes Res Care. 2024 Jun 19;12(3):e004120. doi: 10.1136/bmjdrc-2024-004120.

  PMID: 38901858 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Juliana Chan, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 22, 2019
• First Posted: August 7, 2019
• Study Start: January 14, 2020
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: July 20, 2022

Record last verified: 2022-07

Locations

HK (1)