Personalised Medicine in Pre-diabetes and Early Type 2 Diabetes

NCT ID: NCT03558867

Last Updated: 2024-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 138 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-05
• Study Completion Date: 2024-07-23

Brief 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.

Detailed 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.

Conditions

Pre Diabetes; Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Metformin + Healthy diet

Metformin (1500 mg/d, Extended Release) + Healthy, low fat diet

Group Type: PLACEBO_COMPARATOR

Metformin + Healthy diet

Intervention Type: DRUG

Metformin (1500 mg/d, Extended Release) + Healthy, low fat diet

Metformin + Personalized diet

Metformin (1500 mg/d, Extended Release) + Personalized diet based on an algorithm developed at the Weizmann Institute of Science (Zeevi et al, Cell 2015)

Group Type: ACTIVE_COMPARATOR

Metformin + Personalized diet

Intervention Type: DRUG

Metformin (1500 mg/d, Extended Release) + Algorithm-based personalized diet

Interventions

Metformin + Healthy diet

Metformin (1500 mg/d, Extended Release) + Healthy, low fat diet

Intervention Type: DRUG

Metformin + Personalized diet

Metformin (1500 mg/d, Extended Release) + Algorithm-based personalized diet

Intervention Type: DRUG

Other Intervention Names

Metformin + Healthy (low fat) diet

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Weizmann Institute of Science

OTHER

Sponsor Role: collaborator

Garvan Institute of Medical Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dorit Samocha-Bonet, PhD

Role: PRINCIPAL_INVESTIGATOR

Garvan Institute of Medical Research

Jerry Greenfield, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Garvan Institute of Medical Research

Eran Elinav, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Weizmann Institute of Science

Eran Segal, PhD

Role: PRINCIPAL_INVESTIGATOR

Weizmann Institute of Science

Locations

Garvan Institute of Medical Research

Sydney, New South Wales, Australia

Countries

Australia

References

Htet TD, Godneva A, Liu Z, Chalmers E, Kolobkov D, Snaith JR, Richens R, Toth K, Danta M, Hng TM, Elinav E, Segal E, Greenfield JR, Samocha-Bonet D. Rationale and design of a randomised controlled trial testing the effect of personalised diet in individuals with pre-diabetes or type 2 diabetes mellitus treated with metformin. BMJ Open. 2020 Oct 10;10(10):e037859. doi: 10.1136/bmjopen-2020-037859.

Reference Type: DERIVED

PMID: 33040003 (View on PubMed)

Related Links

https://pubmed.ncbi.nlm.nih.gov/33040003/

Study protocol paper

Other Identifiers

SVH 17/080

Identifier Type: -

Identifier Source: org_study_id