Clinical trial NCT03467763: Trial of an Intervention to Improve Metformin Persistence and Adherence
Official title: Trial of an Intervention to Improve Metformin Persistence and Adherence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Metformin Adverse Reaction
Tolerance
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Agency for Healthcare Research and Quality (AHRQ)
First posted: 2018-03-16
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed description: Results have been presented in a single study arm as the order in which patients received drug or placebo was unique for each patient.

Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

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

Primary outcomes:
measure: Treatment Satisfaction as Measured by the Treatment Satisfaction Questionnaire for Medication (TSQM II)
timeFrame: 4-months
measure: Number of Subjects Able to Tolerate Higher Dose of Metformin,
timeFrame: 6-months
Secondary outcomes:
measure: Change in Score of Gastrointestinal Symptom Rating Scale (GSRS)
timeFrame: Reoccurring every 2-weeks for 4-months
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Leon Igel, MD
role: PRINCIPAL_INVESTIGATOR
References: