Trial Title:
Pragmatic Trial of Metformin for Glucose Intolerance or Increased BMI in Prostate Cancer Patients
NCT ID:
NCT05515978
Condition:
Prostate Cancer
Conditions: Official terms:
Prostatic Neoplasms
Glucose Intolerance
Metformin
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
In this pragmatic trial, a 2-step electronic consent approach to enroll patients in the
metformin + lifestyle modification or lifestyle modification arms will be used. The
initial consent will invite patients to join a cohort to study prostate cancer and it
will describe the general pragmatic framework under which this protocol will take place
with the opportunity for additional trial opportunities. Subsequent consents will be
limited to those who consented to the initial project and are found to be eligible for a
specific trial (e.g. this metformin/lifestyle intervention trial). Within the framework
of this pragmatic trial and electronic self-consent, these subsequent consents will be
more focused and limited to the specific involvement in the arm in which they have been
randomized. This general approach will follow the trials within cohorts paradigm.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Metformin
Description:
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.
Arm group label:
Metformin and Lifestyle Modification Arm
Other name:
Glucophage
Other name:
Riomet
Other name:
Glumetza
Intervention type:
Behavioral
Intervention name:
Lifestyle Modification
Description:
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
Arm group label:
Lifestyle Modification Only Arm
Arm group label:
Metformin and Lifestyle Modification Arm
Summary:
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
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:
1. Provision to sign and date the consent form in MHC or otherwise via Epic.
2. Subjects must have an MHC Account to participate in the study
3. Be a male aged ≥18 years of age on day of signing the informed consent.
4. Impaired glucose tolerance and/or overweight, and appropriate to receive metformin,
meeting at least one of the following in the last year (timing relative to the
consent presentation not start of therapy):
- HbA1c of 5.7 - 6.4 %
- BMI≥25 kg/m^2
5. Have a prostate cancer diagnosis
6. Have a clinical relationship with a participating provider at a UCHealth facility.
Exclusion Criteria:
1. On therapy for diabetes including any of the following alone or in combination
medications (diet controlled or managed diabetes is allowed - e.g.
diagnosis of Diabetes, but without an active prescription for anti-glycemic
medication):
1. Metformin
2. Insulin
3. Glipizide
4. Glyburide
5. Glimepiride
6. Pioglitazone
7. Rosiglitazone
8. Sitagliptin
9. Saxagliptin
10. Linagliptin
11. Alogliptin
12. Canagliflozin
13. Dapagliflozin
14. Empagliflozin
15. Ertugliflozin
16. Liraglutide
17. Dulaglutide
18. Semaglutide
19. Exenatide
20. Lixisenatide
21. Nateglinide
22. Repaglinide
23. Tirzepatide
2. Contraindication for metformin use which include any of the following which are
exclusionary (in Epic will use most recent lab values):
1. Estimated glomerular filtration rate (eGFR) of < 50 ml/minute (calculated
according to the formula utilized within Epic).
2. Known Total Bilirubin ≥3 mg/dL)
3. Diagnosis of fibrosis or cirrhosis of the liver (ICD10: K74)
4. Diagnosis of alcohol related disorders (ICD10: F10)
5. Metformin allergy in Epic (ICD10: T50.995A)
3. Non-English-speaking patient until Spanish language consent form and relevant
materials can be made available. Due to the novel aspect of this trial, we plan to
get some experience in treating approximately the first 50 patients, make any
changes needed in the study operations and then implement a Spanish consent, as
feasible.
4. Taking any medication with a known class D or higher drug interaction with
metformin, including:
1. Cimetidine
2. Dolutegravir
3. Patiromer
4. Ranolazine
5. Tafenoquine
5. The use of any carbonic anhydrase inhibitors since they are a risk factor for lactic
acidosis, including:
1. Topiramate
2. Dichlorphenamide
3. Acetazolamide
4. Methazolamide
5. Dorzolamide
6. Brinzolamide
7. Dichlorphenamide
8. Sultiame
9. Zonisamide
10. Indisulam
6. Any treating investigator concern, related to tolerance, safety, adherence or for
any other reason
Gender:
Male
Gender based:
Yes
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Colorado Research Center
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Contact:
Last name:
Anne Martin
Phone:
7208480657
Email:
anne.c.martin@cuanschutz.edu
Contact backup:
Last name:
Robyn Swing
Phone:
7208480607
Email:
robyn.swing@cuanschutz.edu
Contact backup:
Last name:
Thomas Flaig, MD
Contact backup:
Last name:
Corbin Eule, MD
Contact backup:
Last name:
Sandra Everett, MD
Contact backup:
Last name:
Tyler J Friedrich, MD
Contact backup:
Last name:
Ryan M Lanning, MD
Contact backup:
Last name:
Vignesh Narayanan, MD
Facility:
Name:
UCHealth-Southern Colorado
Address:
City:
Colorado Springs
Zip:
80863
Country:
United States
Status:
Recruiting
Contact:
Last name:
Elizabeth Graf
Email:
elizabeth.graf@uchealth.org
Contact backup:
Last name:
Robert Hoyer
Facility:
Name:
UCHealth-Metro Denver
Address:
City:
Denver
Zip:
80217-3364
Country:
United States
Status:
Recruiting
Contact:
Last name:
Robyn Swing
Phone:
7208480650
Email:
robyn.swing@cuanschutz.edu
Facility:
Name:
UCHealth-Northern Colorado
Address:
City:
Fort Collins
Zip:
80521
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sara Twombly
Phone:
9704911553
Email:
sara.twombly@uchealth.org
Contact backup:
Last name:
Steven Schuster
Start date:
October 17, 2022
Completion date:
November 6, 2036
Lead sponsor:
Agency:
University of Colorado, Denver
Agency class:
Other
Source:
University of Colorado, Denver
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05515978
