Trial of an Intervention to Improve Metformin Persistence and Adherence

NCT03467763 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: 1706018342K08HS023898
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Metformin is a safe and effective first-line drug for type 2 diabetes that is also widely recommended for weight loss and diabetes prevention. But, metformin is associated with gastrointestinal and other side effects which prevent its use in 10-20% of patients and appear to limit the usable dose in others. This study is an N-of-1 trial design that will recruit 20 previously metformin-intolerant patients for re-challenge with metformin in a double-blind scenario. In this setting, 'intolerant' means either unable to take metformin at all, or unable to increase the dose past 1,000 mg despite the treating physician's recommendation to do so. Patients will be assigned to take their baseline medication regimen plus 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course of placebo. Initial treatment, placebo or metformin XR, will be decided randomly. At the end of each two-week treatment period, participants will complete questionnaires assessing overall satisfaction with the medication, gastrointestinal symptoms, and adherence. Six months after the conclusion of the intervention, patients will be asked if they are continuing metformin at a higher dose than upon entry to the trial. This trial has two aims. First, to test the hypothesis that medication satisfaction will be the same during periods of placebo treatment and during periods of treatment with the active drug. The second aim is to test the hypothesis that \> 30% of metformin-intolerant patients in an N of 1 crossover trial are able to tolerate higher-dose metformin at 6-months.

Conditions

Metformin Adverse Reaction; Tolerance

Outcome Measures

Primary Outcomes (2)

• Treatment Satisfaction as Measured by the Treatment Satisfaction Questionnaire for Medication (TSQM II)

  The primary outcome of this portion of the study will be the global satisfaction subscale of the Treatment Satisfaction Questionnaire for Medication (TSMQ II). The TSQM II is a 12-question survey with four satisfaction domains: effectiveness, side effects, convenience and global satisfaction. Each domain is described by a single numeric score. For each of these domains the lowest possible score (less satisfaction, ie a worse outcome) is 0, the highest (more satisfaction, ie a better outcome) is 100. We report this score global satisfaction domain (ie, subscale). (Note that the global satisfaction score is not a synthesis of the various subscales associated with each domain. It is a subscale in its own right comprised of distinct questions.)

  4-months

• Number of Subjects Able to Tolerate Higher Dose of Metformin,

  For aim 2 of this study, the primary objective is to test the hypothesis \> 30% of the patients enrolled in this study are able to tolerate (continue taking) a higher-dose of metformin at 6 months than they were taking at baseline.

  6-months

Secondary Outcomes (1)

• Change in Score of Gastrointestinal Symptom Rating Scale (GSRS)

  Reoccurring every 2-weeks for 4-months

Study Arms (2)

Metformin Hydrochloride Extended Release

ACTIVE COMPARATOR

Patients will be assigned to take their baseline medication regimen plus 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course of placebo.

Drug: Metformin Extended Release Oral Tablet

Placebo

PLACEBO COMPARATOR

Patients will be assigned to take their baseline medication regimen plus 2 weeks of 250 mg per day of placebo, followed by 500 mg placebo, 750 mg, and 1,000 mg placebo with each treatment period separated by a 2-week course of metformin XR in the same increments of dosage.

Drug: Placebo oral capsule

Interventions

Metformin Extended Release Oral Tablet DRUG

Metformin hydrochloride extended release tablets in dosages of 250 mg, 500 mg, 750 mg, and 1,000 mg. Individual encapsulations of metformin will contain dosages of 250 mg or 500 mg.

Metformin Hydrochloride Extended Release

Placebo oral capsule DRUG

Placebo capsule

Placebo

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of diabetes, pre-diabetes, or obesity
• Previously attempted to take metformin for an above indication
• History of metformin intolerance (defined based on treating physician's assessment that a history of metformin intolerance (defined as the inability, due to side effects, to use metformin at the otherwise medically appropriate dose) exists, confirmed by the patient's recollection of the same history)

You may not qualify if:

• Contraindication to metformin (i.e, advanced renal or liver disease, history of metformin attributed lactic acidosis, or advanced heart failure)
• Pregnant women

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Agency for Healthcare Research and Quality (AHRQ): collaborator

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Results Point of Contact

• Title: Dr. James Flory
• Organization: Memorial Sloan Kettering Cancer Center

floryj@mskcc.org

6468883790

Study Officials

• Leon Igel, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Patients, care providers, and investigators will be masked to the identity of the trial medication until the conclusion of the trial, and unblinding.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is an N-of-1 trial design that will recruit 20 previously metformin-intolerant patients for re-challenge with metformin in a double-blind scenario. Patients will be assigned to take their baseline medication regimen plus 2 weeks of 250 mg per day of metformin extended release, followed by 500 mg metformin XR, 750 mg, and 1,000 mg metformin XR with each treatment period separated by a 2-week course of placebo. Initial treatment, placebo or metformin XR, will be decided randomly.

Study Record Dates

• First Submitted: March 5, 2018
• First Posted: March 16, 2018
• Study Start: February 9, 2018
• Primary Completion: February 1, 2020
• Study Completion: August 1, 2020
• Last Updated: December 7, 2020
• Results First Posted: December 7, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)