- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02548741
Evaluation of the Metformin Effect on Methylglyoxal in Patients With Type 2 Diabetes (MET)
Evaluation of the Metformin Scavenging Mechanism on Methylglyoxal in Patients With Type 2 Diabetes Mellitus
Study Overview
Status
Conditions
Detailed Description
A prospective randomized controlled clinical trial of 120 adult patients will be conducted from June 2015 to June 2017 (2 years). Study participants will be recruited from the University of Arizona Medical Center, South Campus clinics (Endocrine clinic, family medicine clinic and general medicine clinic).
Eighty patients with HbA1c* >6.0% will be randomized to receive either metformin or a similar inactive placebo for 6 weeks. The response of these patients will be compared to 40 patients with normal HbA1c <5.6% who will not receive either study medication.
Twenty four-hour urine samples will be analyzed to measure metformin-MG adducted product (IMZ) at baseline (D0) and at the end of the study period (D42). Blood sample will be analyzed at the baseline to measure the plasma methylglyoxal concentration (baseline MG concentration- D0) and re-measure it at the end of the study period(D42). Mass spectrometry will be performed for samples analysis to detect the plasma methylglyoxal (MG) level. Metformin-MG adducted product (IMZ) will be measured using Multiple Reaction Method (MRM). Also, Mass spectrometry will be performed to detect plasma protein modifications at baseline and at the end of the study period (after 6 weeks). Investigators will measure the concentrations of IMZ and MG in the human urine and plasma of our cohort in the nM and μM range, respectively via mass spectrometry. Investigators will be normalizing these values by specific gravity.
A logbook will be provided to each participant to record their blood sugar measurements at home. Investigators will provide glucometer (One Touch glucometer), strips and lancets to patients who never had glucometer before enrolling to our study. Participants taking metformin or placebo will be asked to perform an 4-point self-measured blood sugar profile with measurements taken as indicated in the table (once a week). Investigators will contact study participants (treatment and placebo group only) by phone at the mid of the study period (D21) to follow up on the recorded fasting blood glucose levels and development of side effects. The results of the blood sugar measurements will help the study physicians to adjust diabetes therapy (metformin or the other concomitant diabetes medications) in order that the study subjects maintain appropriate blood glucose control (target pre-meal and bedtime glucose between 90-180 mg/dL).
The participants in the non-diabetic group, they will not receive either metformin hydrochloride or placebo. Their fasting blood glucose, plasma MG level and urine IMZ level will be measured during the study. They will not be required to perform 4 point testing. They will have all the same clinic visits and lab orders as diabetic patients except receiving the study medication.
It is hypothesized that plasma MG level in the metformin treatment group will be less than in the group taking the placebo pills, while there will be no significant difference in MG level between the metformin treatment group and the volunteers without diabetes.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Noha I Ashy, PharmD
- Phone Number: (857)210-8051
- Email: ashy@pharmacy.arizona.edu
Study Contact Backup
- Name: Yulia Abidova, RN
- Phone Number: (520)626-3709
- Email: yabidova@deptofmed.arizona.edu
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Elevated HbA1c > 6.0% (patients with type 2 diabetes mellitus or prediabetes), HbA1C < 9.0%
- For matched non-diabetic patients: HbA1C ≤ 5.6%
- Serum creatinine (SCr) < 1.5 mg/dL in males or < 1.4 mg/dL in females,
- Calculated glomerular filtration rate (GFR) > 60 ml/min/1.73m2,
- Body mass index (BMI) 25-40 kg/m2,
- Glycosylated hemoglobin A1C (HA1C) < 9%,
- No known intolerance to metformin
- Has not taken metformin previous 3 months
Exclusion Criteria:
- Patients on thiazolidinediones (TZD)
- Patients with history of metformin intolerance (gastrointestinal side effects or poor renal function; Serum Cr > 1.5mg/dL in males or > 1.4 mg/dL in females or calculated GFR < 60 mL/min/1.73m2
- Patients with active (symptomatic or unstable) cardiovascular disease
- Patients requiring home oxygen
- Patients with end-stage liver disease (cirrhosis)
- Patients on oral glucocorticoids within the past 30 days (equivalent to prednisone > 5mg/day)
- Excessive alcohol intake (The Substance Abuse and Mental Health Services Administration (SAMHSA) defines heavy drinking as drinking 5 or more drinks on the same occasion on each of 5 or more days in the past 30 days) 29
- Pregnancy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Treatment (Metformin)
Forty patients with elevated glycosylated hemoglobin A1c (HbA1c) > 6.0% (patients with type 2 diabetes mellitus or prediabetes) but HbA1C < 9.0%.
They will receive the active comparator (metformin).
|
Metformin hydrochloride tablets (500-mg) are manufactured by Heritage Pharma INC.
Noha Ashy & David Lee will ground the tablets and put them in capsules to avoid differentiation between treatment and placebo.
Using USP 797 compounding standers, Noha Ashy & David Lee will package the capsules to conceal it from the participants and other investigators.
Compounding will take place at the lab, College of Pharmacy (Darchman building, 2nd floor), University of Arizona.
New empty capsules (size 0, ½ blue-opaque and ½ white-opaque capsule which will be supplied by Letco Medical) will be provided to the treatment (metformin hydrochloride) arm participants that are similar to the placebo (comparator) capsules in term of color and size to conceal placebo from the investigators and participants.
Investigators will provide glucometer (One Touch glucometer), strips and lancets to the treatment and placebo groups.
They will be provided to patients who never had glucometer before enrolling to our study.Also, a logbook will be provided to each participant to record their blood sugar measurements at home.
During visit 2 (day 0) and visit 3 (day 42), urine container will be provided to the study participant for 24-hour urine collection.
Patient will be instructed to bring the container back to the collaboratory.
Investigators will transfer the urine container to Dr.Lau's lab to measure the IMZ concentration/content.
|
Placebo Comparator: Placebo
Forty patients with elevated glycosylated hemoglobin A1c (HbA1c) > 6.0% (patients with type 2 diabetes mellitus or prediabetes) but HbA1C < 9.0%.
They will receive the placebo comparator.
|
Investigators will provide glucometer (One Touch glucometer), strips and lancets to the treatment and placebo groups.
They will be provided to patients who never had glucometer before enrolling to our study.Also, a logbook will be provided to each participant to record their blood sugar measurements at home.
During visit 2 (day 0) and visit 3 (day 42), urine container will be provided to the study participant for 24-hour urine collection.
Patient will be instructed to bring the container back to the collaboratory.
Investigators will transfer the urine container to Dr.Lau's lab to measure the IMZ concentration/content.
Investigators will use powder of calcium carbonate as filler of placebo capsules.
Placebo capsules (size 0,½ blue-opaque and ½white-opaque capsule which will be supplied by Letco Medical),will be provided to the comparator arms' participants that are similar to the metformin hydrochloride capsules in term of color and size to conceal placebo from the investigators and participants.Using USP 797 compounding standers, Noha Ashy & David Lee will package the capsules to conceal it from the participants and other investigators.
Compounding will take place at the lab, College of Pharmacy (Darchman building, 2nd floor), University of Arizona.
|
Other: Non-diabetic
Forty matched non-diabetic patients with HbA1C ≤ 5.6%.
They will not receive either treatment (metformin) or placebo.
|
During visit 2 (day 0) and visit 3 (day 42), urine container will be provided to the study participant for 24-hour urine collection.
Patient will be instructed to bring the container back to the collaboratory.
Investigators will transfer the urine container to Dr.Lau's lab to measure the IMZ concentration/content.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma methylglyoxal (MG) concentration (μM)
Time Frame: Change from baseline in plasma MG concentration at 6 weeks of metformin administration
|
Investigators will measure MG concentration at baseline and after 6 weeks of metformin administration.
An increase in MG has been associated with type-2 diabetes and progression of diabetes complications.
Metformin is a known scavenger of MG, forming a metformin-MG imidazolinone (IMZ) cyclized product.
This unique property of metformin in enhanced reduction of diabetic complications may be related to its MG-scavenging capabilities.
Investigators will measure the concentrations of MG in the human plasma of the cohort in the μM range via mass spectrometry.
Investigators will be normalizing these values by specific gravity.
|
Change from baseline in plasma MG concentration at 6 weeks of metformin administration
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The urine imidazolinone (IMZ) concentration (nM)
Time Frame: Change from baseline in urine IMZ concentration at 6 weeks of metformin administration
|
Metformin is a known scavenger of MG, forming a metformin-MG imidazolinone (IMZ) cyclized product.
This unique property of metformin in enhanced reduction of diabetic complications may be related to its MG-scavenging capabilities.
Investigators will measure the IMZ concentration/content at baseline and after 6 weeks of metformin administration.
Investigators hypothesized that a concomitant elevation in urine IMZ concentration/content is associated with metformin administration.
Investigators will measure the concentrations of IMZ in the human urine plasma of the cohort in the nM range via mass spectrometry.
Investigators will be normalizing these values by specific gravity.
|
Change from baseline in urine IMZ concentration at 6 weeks of metformin administration
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Serrine S Lau, PhD, University of Arizona
- Study Director: Craig Stump, MD, PhD, University of Arizona
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Gastrointestinal Agents
- Calcium-Regulating Hormones and Agents
- Antacids
- Calcium
- Metformin
- Calcium Carbonate
Other Study ID Numbers
- 1506912530
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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