Metformin and Its Impact on the Substances Associated With NO Production in Prediabetes Patients.

NCT03398356 | Completed Phase 4 Results

• 1 other identifier: ST.C310.17.009
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the effect of different doses of metformin on the function of endothelium in people with pre-diabetes. One group of the patients will receive metformin in dose: 1500 mg, the second one will receive 3000 mg/day. The parameters from healthy volunteers will be taken only at the study beginning to compare the test results with the parameters from patients with pre-diabetes. This group will be not treated with metformin (no intervention)

Conditions

PreDiabetes; Impaired Fasting Glucose (IFG); Impaired Glucose Tolerance (IGT)

Keywords

prediabetes; impaired fasting glucose; impaired glucose tolerance; metformin; nitric oxide

Outcome Measures

Primary Outcomes (6)

• Serum Levels of Metformin at Different Time Points

  the serum concentration of the studied drug-metformin

  6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start

• Serum Levels of Arginine at Different Time Points

  arginine serum concentration

  Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start

• Serum Levels of ADMA at Different Time Points

  ADMA- asymmetric dimethylarginine-serum concentration

  before study start; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start

• Serum Levels of SDMA at Different Time Points

  SDMA-symmetric dimethylarginine-serum concentration

  Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start

• Serum Levels of Citrulline at Different Time Points

  serum concentration of the citrulline

  Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start

• Serum Levels of DMA at Different Time Points

  DMA- dimethylamine, serum concentration

  Baseline; 6 weeks from treatment start; 12 weeks from treatment start; 15 weeks from treatment start

Study Arms (3)

group A

OTHER

metformin dose 3 x 500 mg

Drug: Metformin

group B

OTHER

metformin dose 3 x 1000 mg

Drug: Metformin

group C

NO INTERVENTION

healthy volunteers who had basic parameters assessment and blood tests only at the beginning of the study

Interventions

Metformin DRUG

for group A: 12 weeks metformin treatment in a final dose 3 x 500 mg for group B: 3 weeks metformin treatment in a dose 3 x 500 mg, next: 3 weeks metformin treatment in a final dose 3 x 1000mg, next: 3 weeks metformin treatment in a dose 3 x 500 mg.

Also known as: Metformax, Glucophage, Formetic, Siofor

group A; group B

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age: 40-65 years;
• pre-diabetic status based on fasting plasma glucose (FPG) and / or OGTT;
• without metformin before;
• without ischemic heart disease in history;
• without a stroke in a history;
• without PAOD (peripheral arterial occlusive disease) in a history;
• without active cancer in a history

You may not qualify if:

• age \<40 or \>65;
• diabetes;
• taking metformin before study;
• active cancer;
• history of macro-angiopathy (ischemic heart disease, stroke or TIA, PAOD);
• serious gastrointestinal disease that may affect metformin tolerance;
• renal failure with GFR\<45 ml/min/1.73m2;
• alanin transaminase \> 3 x ULN
• age: 40-65 years;
• no carbo-hydrates disturbances (based on fasting plasma glucose (FPG) and/or OGTT);
• without metformin before;
• without ischemic heart disease in history;
• without a stroke in a history;
• without PAOD (peripheral arterial occlusive disease) in a history;
• without active cancer in a history

Sponsors & Collaborators

• Wroclaw Medical University: lead

Study Sites (1)

NZOZ Nowy Dwór

Wroclaw, Lower Silesian Voivodeship, 54-438, Poland

Location

Related Publications (9)

• IDF Clinical Guidelines Task Force. Global Guideline for Type 2 Diabetes: recommendations for standard, comprehensive, and minimal care. Diabet Med. 2006 Jun;23(6):579-93. doi: 10.1111/j.1464-5491.2006.01918.x.

  PMID: 16759299 BACKGROUND

• Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, Zinman B; Professional Practice Committee, American Diabetes Association; European Association for the Study of Diabetes. Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2006 Aug;49(8):1711-21. doi: 10.1007/s00125-006-0316-2. No abstract available.

  PMID: 16802130 BACKGROUND

• Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65.

  PMID: 9742977 BACKGROUND

• Hamed S, Brenner B, Roguin A. Nitric oxide: a key factor behind the dysfunctionality of endothelial progenitor cells in diabetes mellitus type-2. Cardiovasc Res. 2011 Jul 1;91(1):9-15. doi: 10.1093/cvr/cvq412. Epub 2010 Dec 24.

  PMID: 21186243 BACKGROUND

• De Jager J, Kooy A, Lehert P, Bets D, Wulffele MG, Teerlink T, Scheffer PG, Schalkwijk CG, Donker AJ, Stehouwer CD. Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2005 Jan;257(1):100-9. doi: 10.1111/j.1365-2796.2004.01420.x.

  PMID: 15606381 BACKGROUND

• Wisniewski J, Fleszar MG, Piechowicz J, Krzystek-Korpacka M, Chachaj A, Szuba A, Lorenc-Kukula K, Maslowski L, Witkiewicz W, Gamian A. A novel mass spectrometry-based method for simultaneous determination of asymmetric and symmetric dimethylarginine, l-arginine and l-citrulline optimized for LC-MS-TOF and LC-MS/MS. Biomed Chromatogr. 2017 Nov;31(11). doi: 10.1002/bmc.3994. Epub 2017 May 24.

  PMID: 28436051 BACKGROUND

• Sutkowska E, Fortuna P, Wisniewski J, Sutkowska K, Hodurek P, Gamian A, Kaluza B. Low metformin dose and its therapeutic serum concentration in prediabetes. Sci Rep. 2021 Jun 3;11(1):11684. doi: 10.1038/s41598-021-91174-7.

  PMID: 34083618 RESULT

• Sutkowska E, Fortuna P, Kaluza B, Sutkowska K, Wisniewski J, Prof AG. Metformin has no impact on nitric oxide production in patients with pre-diabetes. Biomed Pharmacother. 2021 Aug;140:111773. doi: 10.1016/j.biopha.2021.111773. Epub 2021 May 29.

  PMID: 34062418 RESULT

• Sutkowska E, Fortuna P, Kaluza B, Sutkowska K, Hodurek P, Fleszar MG. The impact of Sample Handling Time on metformin serum concentration. Biomed Pharmacother. 2021 Jan;133:110971. doi: 10.1016/j.biopha.2020.110971. Epub 2020 Nov 25.

  PMID: 33248407 RESULT

MeSH Terms

Conditions

Prediabetic State; Glucose Intolerance

Interventions

Metformin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

We didn't differentiate pts according to sex or gender. Before the study was finished we assessed the correlation between metformin concentration and BMI/ body mass. It was prepared as an additional analysis based on 20 cases (not published yet).

Results Point of Contact

• Title: Dr Edyta Sutkowska
• Organization: Wroclaw Medical University

edytasutkowska@yahoo.com

+48/503077016

Study Officials

• Edyta Sutkowska, PhD

  Wroclaw Medical University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: At the beginning of the study, patients are assigned a number by a nurse and are assigned to group A or B according to ID. When analyzing the results, the researchers only knows the numbers of blood samples.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD; The Head of the Department and Division of Medical Rehabilitation

Model Details: The group of patients taking the drug at the target dose of 3 x 1000 after 4 weeks returned to the dose of 3 x 500 mg. The group of patients taking the drug at the target dose 3 x 500 mg consequently had this dose during the whole study period. The basic parameters and biochemical parameters from healthy individuals at the beginning of the study were assessed to compare with patients with pre-diabetes. This group did not take the metformin and thus did not have further examination and lab-tests during the study.

Study Record Dates

• First Submitted: January 7, 2018
• First Posted: January 12, 2018
• Study Start: October 20, 2017
• Primary Completion: December 30, 2018
• Study Completion: April 30, 2019
• Last Updated: May 27, 2022
• Results First Posted: August 24, 2020

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: the results will be available after the publication of the study
• Access Criteria: data will be available after giving permission by the Investigator

Locations

PL (1)