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Type 2 Diabetes MellitusMETNCT02548741

Evaluation of the Metformin Effect on Methylglyoxal in Patients With Type 2 Diabetes

A study testing Metformin Hydrochloride (500-mg capsule), Glucometer (One Touch glucometer), strips and lancets and Urine container for 24-hour urine collection in people with Type 2 Diabetes Mellitus, run by University of Arizona.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Type 2 Diabetes Mellitus
What is being tested?
Metformin Hydrochloride (500-mg capsule), Glucometer (One Touch glucometer), strips and lancets and Urine container for 24-hour urine collection
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
120 participants
Where
No sites listed yet
Study dates
Sep 2015to Aug 2017
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

No sites are listed yet.

About this study

Official title: Evaluation of the Metformin Scavenging Mechanism on Methylglyoxal in Patients With Type 2 Diabetes Mellitus

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.

Read the 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.

Being tested
Metformin Hydrochloride (500-mg capsule), Calcium carbonate (placebo), Glucometer (One Touch glucometer), strips and lancets, Urine container for 24-hour urine collection
Keywords
Metformin, diabetes, type 2 diabetes, diabetes complications, methylglyoxal, Prediabetes
Medical subject headings
Diabetes Mellitus, Type 2, Diabetes Mellitus, Diabetes Complications, Prediabetic State

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

  • 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.

  • 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.

  • 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.

Study groups in NCT02548741
Study groupRoleWhat they receive
Treatment (Metformin)Active comparatorForty 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).
Receives: Drug: Metformin Hydrochloride (500-mg capsule); Other: Glucometer (One Touch glucometer), strips and lancets; Other: Urine container for 24-hour urine collection
PlaceboPlacebo comparatorForty 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.
Receives: Drug: Calcium carbonate (placebo); Other: Glucometer (One Touch glucometer), strips and lancets; Other: Urine container for 24-hour urine collection
Non-diabeticOtherForty matched non-diabetic patients with HbA1C ≤ 5.6%. They will not receive either treatment (metformin) or placebo.
Receives: Other: Urine container for 24-hour urine collection

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Change from baseline in plasma MG concentration at 6 weeks of metformin administration

Secondary outcomes (1)
  1. The urine imidazolinone (IMZ) concentration (nM)

    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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2015 (estimated)
  2. Study startSep 2015
  3. Primary completionAug 2017 (estimated)
  4. Study completionAug 2017 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02548741
Sponsor's protocol ID
1506912530
Acronym
MET
Status last verified
Aug 2015
First submitted
24 Aug 2015
Last updated
14 Sep 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A study testing Metformin Hydrochloride (500-mg capsule), Glucometer (One Touch glucometer), strips and lancets and Urine container for 24-hour urine collection in people with Type 2 Diabetes Mellitus, run by University of Arizona.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 14 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Noha I Ashy, PharmD ((857)210-8051, ashy@pharmacy.arizona.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma methylglyoxal (MG) concentration (μM) (time frame: Change from baseline in plasma MG concentration at 6 weeks of metformin administration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2015.

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