Incretin Hormones in Type 1 Diabetes Mellitus;Effect of Metformin Treatment

NCT ID: NCT04177303

Last Updated: 2020-02-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-11-29

Study Completion Date

2022-11-29

Brief Summary

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Investigators aim is to conduct an RCT to study the effect of adjunct metformin treatment to insulin monotherapy in patients with type 1 diabetes, targeting the intestinal incretin secretion. The patients will be randomly allocated to metformin or placebo treatment for 4 months

Detailed Description

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Compared to the large armamentarium of antidiabetic agents for Type 2 Diabetes Mellitus (T2DM), the insulinocentric therapeutic approach in Type 1 Diabetes Mellitus (T1DM) has distracted the scientific perspective from the rise of novel therapies. Insulin monotherapy has long overshadowed the overall hormonal dysregulation that demarcates T1DM . In specific, the significance of the gut-derived incretin hormones GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic peptide), which are implicated with glucose metabolism via the gut-pancreatic axis, has been merely addressed.

Investigators' goal in the current protocol is to delineate the glucoregulatory role of incretin hormones in T1DM and the therapeutic advantages of adjunct metformin treatment over insulin monotherapy. In the absence of such knowledge, the development of effective strategies to improve metabolic homeostasis and ameliorate complications in T1DM patients will remain problematic. The central hypothesis of the study is that metformin, as an incretin-secretagogue, will enhance postprandial incretin secretion in T1DM patients, which will be reflected in reduced glucagon secretion and improvement in glycemic volatility. Mechanistic insight will be provided through changes in specific amino acids and metabolites patterns, chronic inflammation and the microbiome composition.

Conditions

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Type 1 Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Pilot, mechanistic, phase 3, randomized, placebo-controlled, parallel designed, double-blinded clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
All pills will be provided as effervescent, pre-scored 1000mg tablets, so that they may easily be dichotomized.Boxes with active drug or placebo will be covered to conceal the identity of the test article. Sponsor will provide covering materials.The unblinded designee will provide the covered boxes to the blinded nurse or blinded investigator who will dispense the pills.Participants will be given study drug diaries, which they will complete during study drug intake.

Study Groups

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Metformin

Patients will continue with their standard insulin therapy and will additionally receive orally metformin 2gr/day.

Group Type ACTIVE_COMPARATOR

Metformin

Intervention Type DRUG

Participants will be randomized to metformin 2000 mg

Placebo

Patients will continue with their standard insulin therapy and will additionally receive placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Participants will be randomized to placebo

Interventions

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Metformin

Participants will be randomized to metformin 2000 mg

Intervention Type DRUG

Placebo

Participants will be randomized to placebo

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 years
* T1DM (Diagnosis of diabetes before the age of 35 years and insulin use within 1 year of diagnosis)
* Treatment with multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII)

Exclusion Criteria

* Any cardiovascular disease within the last 3 months
* NYHA stage 3 or 4 heart failure
* Uncontrolled angina
* Liver failure \[AST\>135 IU/L or ALT\>129IU/L (3 x the upper normal limit)\] • Kidney failure or GFR\<60 ml/min/1.73m2
* Gastrointestinal disease or gastroparesis
* Prior diagnosis of cancer within 2 years
* Other medication that affect glucose metabolism within the last 3 months (metformin, SGLT2, GLP-1 analogues, amylin analogues, systemic glucocorticosteroids)
* Untreated or uncontrolled thyroid disease
* Pregnancy or breastfeeding
* Alcohol consumption \> 2-drinks per day or other substance abuse
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hellenic Institute for the Study of Sepsis

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kotsa Kalliopi, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

1st Internal Medicine Department, AHEPA University Hospital

Locations

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Diabetes Center, 1st Internal Medicine Department, AHEPA University General Hospital of Thessaloniki

Thessaloniki, Thessaloniki, Greece

Site Status RECRUITING

Countries

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Greece

Central Contacts

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Evangelos J Giamarellos-Bourboulis, MD, PhD

Role: CONTACT

+306945521800

Antigoni J Kotsaki, MD,PhD

Role: CONTACT

+306946637164

Facility Contacts

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Kalliopi Kotsa, MD,PhD

Role: primary

+306932045201

Antigoni Z Lalia, MD,MSc

Role: backup

+306980661463

Other Identifiers

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INCREDIBLE-ME

Identifier Type: -

Identifier Source: org_study_id

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