NCT Number: NCT05515978
Metformin is used widely in the treatment of type 2 diabetes. It has off-label indications for use in the prevention of diabetes and in hyperinsulinar obesity. In medical practices, the implementation of metformin for these off-label indications is variable, often at the level of the provider. Multiple retrospective investigations have also shown a clinical benefit in men with prostate cancer who are incidentally treated with metformin.
This pragmatic study will test the feasibility of enrolling patients who have glucose intolerance (as defined by HbA1c of 5.7-6.4%) and/or who have increased BMI (BMI greater than or equal to 25 kg/m2) to a randomized pragmatic study of metformin plus lifestyle modification information versus lifestyle modification information only. For purposes of the scope of this project and the study's feasibility, this will be implemented in a group of prostate cancer patients, who may have additional benefits from metformin.
Interested in participating?
Request Info18 year and older
Male
Interventional
Early Phase 1
Colorado Research Center, Aurora, Colorado, United States
In this study, subjects with prostate cancer will be randomized to metformin plus educational material for lifestyle modification versus educational material for lifestyle modification alone and followed for up to 10 years. Population-based, retrospective studies have reported improved outcomes, including prostate cancer specific mortality, with the incidental use of metformin in prostate cancer patients. One prominent study is this area from Margel, et al was published in 2013.2 Using the administrative database from several Ontario health districts, men aged 66 with incidental diabetes and prostate cancer antigen (PCA) were studied. The study included over 3000 men and found an adjusted hazard ratio of 0.76 (95% CI, 0.64 to 0.89) for PCA-specific mortality for each additional 6 months of metformin use. There was no relationship to survival with any other diabetic medication.
In addition to the use of metformin for the prevention of metabolic complications related to obesity and the prevention of diabetes, there are several studies reporting a potential benefit in those with prostate cancer. In a Veterans Administration-based study, more than 87,000 subjects were identified with PCA in the sample.3 The subjects were analyzed in 3 cohorts: 1) no diabetic medication (DM), 2) DM without metformin use and 3) DM with metformin use. Men with DM who were treated with metformin were found to have improved OS (HR 0.82, 95% CI 0.78 - 0.86, for mortality) compared to men with DM not on metformin. Reduced cancer specific mortality was also observed in the men with DM on metformin (HR 0.70, 95% CI 0.64 -0.77) in comparison to men with DM not taking metformin (HR 0.93, 95% CI 0.85 -1.00) - the reference group were those without DM. Despite considerable interest in these findings, there is little if any prospective data on the use of metformin in this setting.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
In order to be eligible to participate in this study, an individual must meet all of the following criteria. The patients will be screening for eligibility and offered an electronic consent via the Epic medical record and the patient portal (My Health Connection - MHC) or otherwise through Epic:
Exclusion criteria
diagnosis of Diabetes, but without an active prescription for anti-glycemic medication):
Metformin is a medication used to treat type 2 diabetes, gestational diabetes, and prediabetes. In this study, patients on the Metformin arm will be started on 850 mg daily for 2 weeks, then escalated to a final dose of 850 mg twice daily, which is lower than the maximum recommended dose of 2550 mg total daily.
Other names: Glucophage, Riomet, Glumetza
Patients randomized to this arm will receive standard lifestyle modification recommendations. This will include the general recommendation to increase exercise level mildly, after discussing with the medical provider. There is a potential low-level risk in increasing one's exercise levels.
Here are some examples of the educational material from the American Diabetes Association website, and topics will be rotated on quarterly basis:
Healthy eating: https://www.diabetes.org/nutrition/healthy-food-choices-made-easy Prediabetes: https://www.diabetes.org/diabetes-risk/prediabetes Fitness: https://www.diabetes.org/fitness/get-and-stay-fit Weight loss: https://www.diabetes.org/fitness/weight-loss
Time frame: 4 years
Once there are 6 months of follow-up data on the first 100 patients, a formal analysis will be done to determine the completeness of data and the potential for a powered study. Outcome measure was amended January 2025.
Time frame: 2 years
Metabolic response. Key metabolic parameters assessed as part of routine care:
Body Mass Index (BMI)
Time frame: 2 years
Metabolic response. Key metabolic parameter assessed as part of routine care:
Weight
Time frame: 2 years
Metabolic response. Key metabolic parameters assessed as part of routine care:
HbA1C
Time frame: 2 years
Metabolic response. Key metabolic parameters assessed as part of routine care:
blood pressure
Time frame: 2 years
Metabolic response. Key metabolic parameters assessed as part of routine care:
random glucose level.
Time frame: 2 years
Metabolic response. Key metabolic parameter assessed as part of routine care:
Body Mass Index (BMI)
Time frame: 2 years
Metabolic response. Key metabolic parameters assessed as part of routine care:
Weight
Time frame: 2 years
Metabolic response. Key metabolic parameters assessed as part of routine care:
HbA1C
Time frame: 2 years
Metabolic response. Key metabolic parameters assessed as part of routine care:
blood pressure
Time frame: 2 years
Metabolic response. Key metabolic parameters assessed as part of routine care:
random glucose level.
Time frame: 2 years
Metabolic response. Key metabolic parameters assessed as part of routine care:
1b: Initiation of any additional diabetes medication, and new diagnoses of diabetes. All new diagnoses of diabetes will be reviewed by the adjudication committee
Time frame: 2 years
Metabolic response. Key metabolic parameters assessed as part of routine care:
Initiation of any additional diabetes medication
Time frame: 2 years
Metabolic response. Key metabolic parameters assessed as part of routine care:
New diagnoses of diabetes. All new diagnoses of diabetes will be reviewed by the adjudication committee
Time frame: 2 years
All major adverse cardiac events will undergo chart review and categorized as major cardiac and limb events (MI, stroke, CV death, acute limb ischemia, major vascular amputation).
Time frame: 2 years
All major adverse cardiac events will undergo chart review and categorized as major cardiac and limb events (MI, stroke, CV death, acute limb ischemia, major vascular amputation).
Time frame: 2 years
PSA doubling as surrogate for progression, defined using a modified approach from the prostate cancer working group 3(PCWG 2016)1.. First all PSA values less than 1 ng/dL will be set to 1 ng/dL. If this PSA value is 1 ng/dL an event (i.e., PSA doubling or death) will be defined as the next PSA value that was greater than or equal to 2 ng/dL or death. Alternatively, if a patient's first PSA is greater than 1 ng/dL the nadir was identified. If the variability in PSA values prior to the nadir is low (i.e., there was less than a 5% difference between the nadir and previous PSA values) the first value prior to the nadir that is within 5% will be selected as the baseline PSA. An event will be defined as the next PSA value that was greater or equal to 2 times the baseline PSA or death. Patients that never experienced a PSA doubling or death will be censored at their last known PSA measurement.
Time frame: 2 years
A modified PSA biochemical response: PSA response defined as a ≥50% decline in PSA from the baseline level at the start of the study. The study-associated provider will receive a clinical decision support query with any PSA response observed: "Is it likely that any other intervention such as additional medical or local therapy besides metformin may have caused the subjects recent PSA response?"
Time frame: 10 years
Following every scan, the study associated provider will be asked "Does the subject have evidence of radiographic progression in your opinion"
Time frame: 10 years
Overall and prostate cancer specific mortality: The Colorado State Death Registry, which is integrated with Health Data Compass (HDC), will be used to determine the overall survival status. The subject's trial-associated provider will receive a clinical decision support query from the study regarding any subject who dies on the trial: "Did this subject die due to complications of prostate cancer?" (Investigator assessment). Every death will be chart reviewed.
Time frame: 2 years
Safety endpoints via HDC (death, hospitalization, and metformin-associated lactate level elevation diagnosis codes frequency). Lab values, such as a lactate level, may also be utilized for specific diagnosis. The PI and steering committee will review these on a regular basis any notify the IRB with a notable difference between the arms. Metformin-associated lactic acidosis will specifically be an AE of interest.
Time frame: 2 years
The number, proportion, and demographics of eligible patients: eligible patients include those deemed eligible to receive a consent in MHC/Epic through assessment of the demographic information. The proportion will be determined by dividing the number of patients who sign the second consent by those who received the first consent. The demographics of those who signed the second consent will be compared with those who signed the initial consent.
Time frame: 2 years
Accuracy of Epic screening process: The charts of the first 50 patients identified by Epic will be reviewed manually by the PI and study team.
Time frame: 2 years
The consent completion rate as determined by the electronic signature of the consent in MHC/Epic within one month of availability or posting and also at any timepoint thereafter (early versus late completion).
Time frame: 2 years
Study Enrollment: The number of patients who sign the second consent (consent #2 or #3) in MHC/Epic will be counted toward study accrual and the time it takes to enroll 100 will be assessed.
Time frame: 2 years
Accuracy of TriNetX estimates of eligible patients, including filtering for appointments with participating providers, will be compared with the number of consents released in MHC/Epic monthly.
Time frame: 10 years
The proportion of patients with active metformin prescription at one year after enrollment and then annually will be assessed. The number of patients in the non-metformin arm who start metformin and/or another anti-diabetes medication during the study period will be assessed.
Contact information is provided by the study sponsor or research team.
Emily Buchanan
CONTACT
Marjorie McIntyre
CONTACT
University of Colorado, Denver
Other
A Randomized, Pragmatic, Adaptive Trial of Metformin for Glucose Intolerance or Increased Body Mass Index in Prostate Cancer Patients
Acronym: PragMet
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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