Diet Change for Metabolic Dysfunction in Colorectal Polyp Patients

(REMEDY Trial)

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of South Carolina

Must not be taking: Antibiotics

Disqualifiers: Comorbid conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6 months

180 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a 6-month randomized controlled trail of diet modification designed to reduce chronic inflammation and reverse metabolic dysfunction among obese individuals with one or more polyps found at a colonoscopy screening. We also will recruit an at least overweight partner, who lives in the same household. To be eligible, participants will be apparently disease-free, obese AAs or EAs who have self-identified a partner who is at least 9 years, with whom they live and who also is at least overweight. Each index participant will: 1) Be AA or EA by self-report; 2) Be ≤55 years old; 3) Have undergone a colonoscopy screening and found to have ≥1 polyp(s); 4) Be free of co-morbid conditions or other factors that would limit participation in this trial; 5) Have a BMI ≥30kg/m2; 6) Be willing to commit to investing the time and effort required to participate in this trial (i.e., willing to complete all assessments and provide biological samples as specified in the consent); and 7) Have no recent antibiotic use. Their partner needs to: 1) Be at least 9 years old; 2) Live in the same household and consumes meals together; 3) Be at least overweight; 4) Agree to all study procedures, including provision of biological samples, body measurements, and self-reported dietary and other assessments; and 5) Have no recent antibiotic use.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that participants should not have used antibiotics recently (within the last 3 months).

What data supports the effectiveness of the drug IMAGINE HEALTHY and its components for metabolic dysfunction in colorectal polyp patients?

Research suggests that metformin, a component of the drug, may have a protective role against colorectal cancer and its precursors in diabetic patients, potentially reducing cancer-related deaths. However, a study on familial adenomatous polyposis (FAP) patients found that metformin did not significantly reduce the number or size of polyps. ^{1 2 3 4 5}

Is metformin safe for humans?

Metformin is generally considered safe for humans when used as directed, especially for managing type 2 diabetes. It has a low risk of causing low blood sugar and does not lead to weight gain, but it is important to monitor kidney and liver function to avoid serious side effects. ^{6 7 8 9 10}

How does the drug IMAGINE HEALTHY (metformin) differ from other treatments for colorectal polyps?

IMAGINE HEALTHY, also known as metformin, is unique because it is primarily a diabetes medication that may have a protective role against colorectal polyps by activating AMPK (a protein that helps regulate energy balance) and inhibiting mTOR (a protein involved in cell growth), which could potentially suppress polyp growth. ^{1 3 4 11 12}

Eligibility Criteria

This trial is for disease-free, obese African Americans or European Americans under 55 years old with at least one polyp found during colonoscopy. They must have a BMI of ≥30kg/m2 and a partner who is at least overweight and shares meals with them. Both should not have used antibiotics recently.

Inclusion Criteria

Free of co-morbid conditions or other factors that would limit participation in this trial

I have polyps found during a colonoscopy that increase my risk for future cancer.

AA or EA by self-report

Exclusion Criteria

N/A

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a 6-month dietary intervention with weekly classes for 12 weeks and monthly classes for 3 months, including cooking, movement, and stress reduction

6 months

3 visits (in-person) at baseline, 3 months, and 6 months; weekly classes for 12 weeks; monthly classes for 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of microbiome and metabolic markers

4 weeks

Treatment Details

Interventions

• IMAGINE HEALTHY

Trial Overview The 'IMAGINE HEALTHY' program focuses on diet modification to reduce inflammation and reverse metabolic dysfunction in obese individuals with colorectal polyps and their overweight partners over a period of six months.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

Participation will be for six months. Participants will meet staff at three timepoints (baseline, 3 months, 6 months) to complete questionnaires, online dietary assessment, body measures, have blood pressure measured, provide blood and stool samples, and wear an activity monitor for a week at each time point. In addition, participants will attend weekly classes for 12 weeks and one class per month for three months. These classes will include cooking, movement, and stress reduction.

Group II: Comparison Active Control 1 Intervention

Participation will be for six months. Participants will meet staff at three timepoints (baseline, 3 months, 6 months) to complete questionnaires, online dietary assessment, body measures, have blood pressure measured, provide blood and stool samples, and wear an activity monitor for a week at each time point.

IMAGINE HEALTHY is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Metformin for:

• Type 2 Diabetes
• Polycystic Ovary Syndrome

Approved in Canada as Metformin for:

• Type 2 Diabetes
• Polycystic Ovary Syndrome

Approved in European Union as Metformin for:

• Type 2 Diabetes
• Polycystic Ovary Syndrome

Who Is Running the Clinical Trial?

University of South Carolina

Lead Sponsor

Trials

233

Recruited

122,000+

Findings from Research

In a study of 401 diabetic patients, those treated with metformin for over 5 years had a significantly lower number of colorectal polyps compared to those on other antidiabetic medications, suggesting a potential protective effect of metformin against polyp formation.

While metformin showed a trend towards lower rates of polyp detection, there were no significant differences in the prevalence of adenomas, high-risk adenomas, or colorectal cancer between the metformin and control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Metformin Associated with a Lower Prevalence of Polyps, Adenomas, and Colorectal Carcinoma in Patients with Diabetes Mellitus? Canha, MI., Ramos, G., Prata, R., et al.[2023]

In a study of 424 colorectal cancer patients with type II diabetes, those treated with metformin had a significantly longer overall survival of 76.9 months compared to 56.9 months for those not on metformin, indicating its potential benefit in cancer outcomes.

The analysis showed that metformin treatment was associated with a 30% improvement in overall survival compared to other diabetes medications, suggesting that it may play a protective role in colorectal cancer patients with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival advantage observed with the use of metformin in patients with type II diabetes and colorectal cancer. Garrett, CR., Hassabo, HM., Bhadkamkar, NA., et al.[2022]

In a study of 58 acromegalic patients, those treated with metformin had a significantly lower prevalence of colonic polyps (24%) compared to those not treated with metformin (57%), suggesting a potential protective effect of metformin against polyp development.

The analysis indicated a strong negative association between metformin intake and the presence of colonic polyps, with an odds ratio of 0.22, highlighting the need for further research to confirm these findings in larger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible protective role of metformin therapy on colonic polyps in acromegaly: an exploratory cross-sectional study. Albertelli, M., Nazzari, E., Dotto, A., et al.[2022]

In a randomized controlled trial involving 34 patients with familial adenomatous polyposis (FAP), metformin treatment (500 mg or 1,500 mg daily for 7 months) did not significantly reduce the number or size of colorectal and duodenal polyps compared to placebo.

Although metformin did not show efficacy in reducing polyp burden, it was associated with lower mTOR signaling in removed polyps, suggesting a potential mechanism of action that may not translate to clinical benefit in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Metformin in Treatment of Adenomas in Patients with Familial Adenomatous Polyposis. Park, JJ., Kim, BC., Hong, SP., et al.[2022]

In a study of over 39,000 Medicare beneficiaries, the initiation of dipeptidyl peptidase-4 inhibitors (DPP-4i) showed no significant association with an increased risk of colorectal cancer, suggesting these medications are safe in this regard.

Similarly, glucagon-like peptide-1 receptor agonists (GLP-1ra) also did not demonstrate a short-term effect on colorectal cancer incidence compared to long-acting insulin, indicating that incretin-based therapies may not pose a heightened cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on colorectal cancer incidence and its precursors. Htoo, PT., Buse, JB., Gokhale, M., et al.[2023]

The combination tablet of sitagliptin and metformin (Janumet) has been approved by the FDA for patients with Type 2 diabetes who need better glycemic control, either when taking these medications separately or together.

Sitagliptin has been demonstrated to be safe and effective at a daily dose of 100 mg, and its combination with metformin is believed to enhance glycemic control through complementary mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janumet: a combination product suitable for use in patients with Type 2 diabetes. Reynolds, JK., Neumiller, JJ., Campbell, RK.[2019]

Metformin is an effective oral medication for treating non-insulin-dependent diabetes mellitus (type II diabetes) and does not cause hypoglycemia, which is a common side effect of other diabetes medications like sulfonylureas.

The drug is considered safe when proper precautions are taken, including monitoring liver and kidney function, and it has gained widespread use internationally, recently receiving FDA approval under the brand name Glucophage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin: a biguanide. Tanja, JJ., Langlass, TM.[2013]

Metformin is a first-line treatment for type 2 diabetes due to its effectiveness in reducing insulin resistance without causing weight gain or hypoglycemia, making it a safe option for patients.

Recent studies have shown that metformin also has cardiovascular benefits and may help in conditions beyond diabetes, such as insulin resistance and potentially tumor suppression, highlighting its broader therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin therapy and clinical uses. Scarpello, JH., Howlett, HC.[2022]

In a study of 78 patients with uncontrolled type 2 diabetes, dapagliflozin showed the most significant reduction in HbA1c levels after 24 months, with a mean change of -1.05%, compared to sitagliptin (-0.81%) and lobeglitazone (-1.08%).

Dapagliflozin also improved body composition by decreasing whole body fat percentage and increasing muscle percentage, while sitagliptin and lobeglitazone led to increases in body fat, suggesting dapagliflozin may be a better option for patients looking to improve their body composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of therapeutic efficacy and safety of sitagliptin, dapagliflozin, or lobeglitazone adjunct therapy in patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea and metformin: Third agent study. Hong, JH., Moon, JS., Seong, K., et al.[2023]

In a study of 305 patients with type 2 diabetes, the combination of glimepiride and metformin resulted in a greater reduction in HbA1c levels (0.42%) compared to the sitagliptin and metformin combination (0.30%) after 12 weeks, indicating better glycemic control with glimepiride.

Both treatment groups showed similar changes in body mass index (BMI) and comparable rates of hypoglycemic events, suggesting that glimepiride is effective without increasing the risk of low blood sugar or affecting weight significantly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Evaluation of Safety and Efficacy of Glimepiride and Sitagliptin in Combination with Metformin in Patients with Type 2 Diabetes Mellitus: Indian Multicentric Randomized Trial - START Study. Devarajan, TV., Venkataraman, S., Kandasamy, N., et al.[2022]

In a study using Apc(Min/+) mice, metformin significantly reduced the number of larger intestinal polyps (over 2 mm) but did not affect the total number of polyps, indicating a targeted effect on polyp growth rather than overall formation.

Metformin's mechanism of action involves activating AMPK, which inhibits the mammalian target of rapamycin (mTOR) pathway, suggesting its potential as a chemopreventive agent for colorectal cancer despite not significantly altering insulin resistance or serum lipid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin suppresses intestinal polyp growth in ApcMin/+ mice. Tomimoto, A., Endo, H., Sugiyama, M., et al.[2013]

In a study of 3,505 type 2 diabetes patients, those with diabetes had a higher prevalence of adenomatous polyps (62.8%) compared to non-diabetic controls (53.6%), indicating a potential link between diabetes and more aggressive polyp formation.

Factors such as male gender, age, and BMI were identified as independent risk factors for having multiple polyps in diabetic patients, suggesting that older male patients with higher BMI should be prioritized for colonoscopy screenings to reduce colorectal cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Korean type 2 diabetes patients have multiple adenomatous polyps compared to non-diabetic controls. Suh, S., Kang, M., Kim, MY., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Is Metformin Associated with a Lower Prevalence of Polyps, Adenomas, and Colorectal Carcinoma in Patients with Diabetes Mellitus? [2023]

2. England pubmed.ncbi.nlm.nih.gov

Survival advantage observed with the use of metformin in patients with type II diabetes and colorectal cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Possible protective role of metformin therapy on colonic polyps in acromegaly: an exploratory cross-sectional study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

The Effect of Metformin in Treatment of Adenomas in Patients with Familial Adenomatous Polyposis. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Effect of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on colorectal cancer incidence and its precursors. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Janumet: a combination product suitable for use in patients with Type 2 diabetes. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Metformin: a biguanide. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Metformin therapy and clinical uses. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Comparison of therapeutic efficacy and safety of sitagliptin, dapagliflozin, or lobeglitazone adjunct therapy in patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea and metformin: Third agent study. [2023]

10. India pubmed.ncbi.nlm.nih.gov

Comparative Evaluation of Safety and Efficacy of Glimepiride and Sitagliptin in Combination with Metformin in Patients with Type 2 Diabetes Mellitus: Indian Multicentric Randomized Trial - START Study. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Metformin suppresses intestinal polyp growth in ApcMin/+ mice. [2013]

12. Korea (South) pubmed.ncbi.nlm.nih.gov

Korean type 2 diabetes patients have multiple adenomatous polyps compared to non-diabetic controls. [2021]