NCT02548741

Brief Summary

This study is designed to investigate the effects of metformin, a commonly prescribed first line medication for diabetes and recommended for prediabetes, on the levels of the potentially tissue damaging reactive product (MG) in the blood and its cleared counterpart in the urine (IMZ). The study will involve patients with elevated HbA1c randomized to receive either metformin or a similar inactive placebo pill and a group of sex and age matched volunteers without diabetes. 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 normal HbA1c \<5.6% who will not receive either study medication. Investigators will compare the plasma MG and urine IMZ concentration/content between the 3 groups before and after the 6-week intervention. 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.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
120

participants targeted

Target at P50-P75 for not_applicable type-2-diabetes-mellitus

Timeline
Completed

Started Sep 2015

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 24, 2015

Completed
8 days until next milestone

Study Start

First participant enrolled

September 1, 2015

Completed
13 days until next milestone

First Posted

Study publicly available on registry

September 14, 2015

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2017

Completed
Last Updated

September 14, 2015

Status Verified

August 1, 2015

Enrollment Period

1.9 years

First QC Date

August 24, 2015

Last Update Submit

September 10, 2015

Conditions

Type 2 Diabetes Mellitus

Keywords

Metformindiabetestype 2 diabetesdiabetes complicationsmethylglyoxalPrediabetes

Outcome Measures

Primary Outcomes (1)

  • Plasma methylglyoxal (MG) concentration (μM)

    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 Outcomes (1)

  • The urine imidazolinone (IMZ) concentration (nM)

    Change from baseline in urine IMZ concentration at 6 weeks of metformin administration

Study Arms (3)

Treatment (Metformin)

ACTIVE COMPARATOR

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).

Drug: Metformin Hydrochloride (500-mg capsule)Other: Glucometer (One Touch glucometer), strips and lancetsOther: Urine container for 24-hour urine collection

Placebo

PLACEBO COMPARATOR

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.

Drug: Calcium carbonate (placebo)Other: Glucometer (One Touch glucometer), strips and lancetsOther: Urine container for 24-hour urine collection

Non-diabetic

OTHER

Forty matched non-diabetic patients with HbA1C ≤ 5.6%. They will not receive either treatment (metformin) or placebo.

Other: Urine container for 24-hour urine collection

Interventions

Metformin Hydrochloride (500-mg capsule)DRUG

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.

Treatment (Metformin)
Calcium carbonate (placebo)DRUG

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.

Placebo
Glucometer (One Touch glucometer), strips and lancetsOTHER

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.

PlaceboTreatment (Metformin)
Urine container for 24-hour urine collectionOTHER

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.

Non-diabeticPlaceboTreatment (Metformin)

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Diabetes MellitusDiabetes ComplicationsPrediabetic State

Interventions

MetforminCalcium CarbonateUrine Specimen Collection

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic ChemicalsCalcium CompoundsInorganic ChemicalsCarbonatesCarbonic AcidCarbon Compounds, InorganicMineralsSpecimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisInvestigative Techniques

Study Officials

  • Serrine S Lau, PhD

    University of Arizona

    PRINCIPAL INVESTIGATOR

  • Craig Stump, MD, PhD

    University of Arizona

    STUDY DIRECTOR

Central Study Contacts

Noha I Ashy, PharmD

CONTACT

(857)210-8051ashy@pharmacy.arizona.edu

Yulia Abidova, RN

CONTACT

(520)626-3709yabidova@deptofmed.arizona.edu

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, Department of Pharmacology and Toxicology

Study Record Dates

First Submitted

August 24, 2015

First Posted

September 14, 2015

Study Start

September 1, 2015

Primary Completion

August 1, 2017

Study Completion

August 1, 2017

Last Updated

September 14, 2015

Record last verified: 2015-08