Personalised Medicine in Pre-diabetes and Early Type 2 Diabetes

Type 2 Diabetes Mellitus Clinical Trial

— PREDICT  

Official title:

Personalised Medicine in Prediabetes - Towards Preventing Diabetes in Individuals at Risk

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03558867
• Other study ID #: SVH 17/080
• Status: Active, not recruiting
• Phase: N/A
• Start date: June 5, 2018
• Est. completion date: July 30, 2024

Study information

• Verified date: August 2023
• Source: Garvan Institute of Medical Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Prediabetes is a common condition in overweight individuals affecting approximately 35% of American adults and 30% of Australian adults. Like diabetes, prediabetes is a serious risk factor for cardiovascular disease, eye, kidney and liver disease, and some types of cancer.

Appropriate blood glucose control is crucial in preventing pre-diabetes complications and onset of diabetes, yet clinical practice, backed by randomised trials, reports that many patients treated with standard dietary guidelines or with the first-line treatment of diabetes patients, metformin, do not improve blood glucose control sufficiently.

The overarching goal of the present project is to improve the efficacy of metformin mono-therapy in pre-diabetes and early type 2 diabetes.

Description:

Prediabetes is common in overweight and obese individuals and, as with frank diabetes, it is a risk factor for cardiovascular disease, cognitive dysfunction, fatty liver, kidney, ophthalmic, renal and neuropathic disease, and cancer.

Effective management of dysglycemia in pre-diabetes and diabetes and prevention of diabetes in individuals at risk reduce the risk of organ damage and associated co-morbidities and improves the affected individuals' quality of life.

Metformin, an oral biguanide, is the first-line treatment of newly-diagnosed type 2 diabetes patients, and the pharmacological choice for preventing diabetes in individuals with pre-diabetes. Metformin is an ideal medication to initiate for diabetes prevention, due to its excellent safety profile (lack of hypoglycemia), neutral to marginally beneficial effect on body weight, evidence of cardio-protection, and low cost. However, clinical practice, backed by randomised clinical trials, suggests that metformin mono-therapy fails to achieve glycemic goals in 20-40% of type 2 diabetes patients and to prevent diabetes in approximately 20% of individuals with pre-diabetes.

While the mode of action of metformin is still being investigated, the liver and the gastrointestinal tract are thought to be the main targets responsible for the improvement in glycemia. An increasing body of evidence suggests that the gut microbiota play an important role in obesity, prediabetes and diabetes, and alterations in gut microbial composition have been described in individuals with type 2 diabetes and pre-diabetes. Interestingly, metformin-treated diabetes patients have a "healthier" gut microbial composition compared with treatment-naïve diabetes patients, and changes in gut microbial composition with metformin treatment has been suggested to contribute to the therapeutic effect of the medication.

Randomised, clinical study with parallel assignment and single-masking will be performed in treatment-naïve individuals with pre-diabetes or early type 2 diabetes (diagnosed in the last 6 months) aiming to compare the effect of metformin (extended release [XR]) 1500 mg/d administered with personalized diet (based on the Weizmann Institute Personalized Nutrition Project) or administered with a healthy (low fat) diet.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 264
• Est. completion date: July 30, 2024
• Est. primary completion date: July 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 70 Years

Eligibility

Inclusion criteria:

• Individuals with pre-diabetes or newly-diagnosed (in the last 6 months) with type 2 diabetes, fulfilling the following criteria:

• Impaired fasting glucose (IFG, plasma glucose [PG]- 5.6 - 6.9 mmol/L, ±0.2 mmol/L) and/or impaired glucose tolerance (IGT, 2-h PG 7.8 - 11.0 mmol/L, ±0.2 mmol/L) with or without elevated HbA1c (up to 8.0 %).

• Willingness to provide written informed consent and willingness to participate and comply with the study.

Exclusion Criteria:

• Females planning a pregnancy during the course of the research or 3 months after completion of the research project.

• Patients with type 1 diabetes, chronically active inflammatory disease, neoplastic disease in the previous 3 years, chronic gastrointestinal disorders, including inflammatory bowel disease or celiac.

• Liver enzymes ALT and/or AST>3-times normal range limit.

• Abnormal renal function as measured by (eGFR<45 mL/min/1.73m^2).

• Individuals with a history of a psychological illness or condition that may interfere with the individual's ability to understand the requirements of the study.

• Normo-glycaemia.

• HbA1c>8.0%

• Cardiovascular event in the previous 6 months.

• Current or recent (within 24 months) treatment with a glucose lowering medication (i.e. GLP-1 receptor agonist, SGLT2 inhibitor, thiazolidinedione, sulfonylurea, DPP-4 inhibitor or insulin).

• Current or recent (within 3 months) treatment with metformin.

• Treatment with an oral steroid.

• Treatment with antibiotics/antifungal in the last 3 month.

• Treatment with immunosuppressive medications.

• Alcohol or substance abuse.

• Participants who had received an investigational new drug within the last 6 months.

• Participants involved in another clinical study.

• Participants who actively lose weight.

• Participants who had a bariatric surgery.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Metformin + Healthy diet
Metformin (1500 mg/d, Extended Release) + Healthy, low fat diet
• Metformin + Personalized diet
Metformin (1500 mg/d, Extended Release) + Algorithm-based personalized diet

Locations

Country	Name	City	State
Australia	Garvan Institute of Medical Research	Sydney	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
Garvan Institute of Medical Research	Weizmann Institute of Science

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Gut microbiome (exploratory)	Difference in gut microbiome features between the groups	6 months
Primary	Mean change in glycated haemoglobin (HbA1C, %) from baseline	Difference in the reduction of HbA1C between the groups	6 months
Secondary	Total daily time of interstitial glucose levels below 7.8 mmol/L (140 mg/dL)	Difference in the time (minutes) per day with interstitial glucose measured below 7.8 mmol/L (140 mg/dL) between the groups	6 months
Secondary	Glycaemic variability	Difference in the glycaemic variability as derived from CGM between the groups	6 months
Secondary	Body weight	Difference in the magnitude of weight loss between the groups	6 months
Secondary	Body fat mass	Difference in body fat mass composition as assessed using dual-energy X-ray absorptiometry (DXA) between the groups	6 months
Secondary	Abdominal visceral fat volume	Difference in the abdominal visceral fat volume as assessed using DXA between the groups	6 months
Secondary	Serum low-density lipoprotein (LDL)-cholesterol concentration	Difference in serum LDL-cholesterol between the groups	6 months
Secondary	Serum high-density lipoprotein (HDL)-cholesterol concentration	Difference in serum HDL-cholesterol concentration between the groups	6 months
Secondary	Serum triglycerides concentration	Difference in serum triglycerides between the groups	6 months
Secondary	Blood pressure	Difference in diastolic and systolic blood pressure between the groups	6 months
Secondary	Liver fat	Difference in liver fat measured by the Fibroscan's controlled attenuation parameter (CAP) function between the groups	6 months