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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how a specific diet change can reduce inflammation and improve metabolic health in individuals who are obese and have had one or more polyps found during a colonoscopy. Participants will either follow a regular plan or attend classes on cooking, movement, and stress reduction for six months. Suitable candidates include individuals who are obese, have had a colonoscopy showing polyps, and live with an overweight partner. Both participants and their partners must be willing to complete various assessments and provide samples throughout the study. As an unphased study, this trial offers a unique opportunity to contribute to groundbreaking research that could improve health outcomes for many.

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 prior data suggests that this diet modification is safe for participants?

Research shows that the IMAGINE HEALTHY diet change in this study aims to reduce chronic inflammation and improve metabolic health. Although specific studies on the safety of this diet change are lacking, its drug-free nature suggests it should be well-tolerated. Generally, changing one's diet is safe for most people, especially when it emphasizes healthy eating.

This trial is labeled as "Not Applicable" for phases, indicating it doesn't involve a new drug or device requiring strict safety testing. Instead, it focuses on lifestyle changes, which typically present fewer safety concerns than medications.

In summary, the safety of a diet-based approach like this is expected to be good, as it involves natural changes to eating habits rather than new drugs. Participants can feel confident about the general safety of trying a structured diet change program. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a comprehensive lifestyle intervention approach for managing metabolic dysfunction in patients with colorectal polyps. Unlike standard treatments that might focus on medication or surgical options, this trial emphasizes the potential benefits of diet, exercise, and stress reduction. Participants in the intervention group will attend cooking and movement classes, which could empower them with sustainable lifestyle changes. By integrating these aspects, researchers hope to uncover how lifestyle adjustments can directly influence metabolic health and potentially reduce the recurrence of colorectal polyps.

What evidence suggests that this diet change is effective for reducing metabolic dysfunction in colorectal polyp patients?

This trial will compare the effects of dietary changes on metabolic dysfunction in patients with colorectal polyps. Research has shown that dietary changes can significantly reduce long-term inflammation and improve overall health. Studies have found that healthier eating can lower the risk of developing new colon growths, known as polyps. This is particularly important for individuals who are overweight and have previously had polyps detected during a colonoscopy. Consuming more whole foods, reducing fat intake, and increasing fiber can enhance gut health and may help prevent additional polyps from forming. Early findings also suggest that these lifestyle changes can aid in weight management and boost long-term health. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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 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]

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 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]

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]

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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11235560/

Metformin administration in prevention of colorectal polyps ... Metformin use and colorectal polyp incidence in type 2 DM patients showed a negative correlation, independent of the hypoglycemic effect of metformin.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4204699/

Does Metformin Affect The Incidence of Colonic Polyps and ... The Colorectal polyp detection rate was lower in the metformin group than in the non-meformin group (39.4% vs. 62.4%, P<0.01). Colorectal adenoma detection rate ...

3. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/1471-2407-12-118

Metformin efficacy and safety for colorectal polyps - BMC Cancer We devised a prospective randomized controlled trial to evaluate the chemopreventive effect of metformin against metachronous colorectal polyps.

4. mdpi.com mdpi.com/1422-0067/26/13/6040

Metformin in Colorectal Cancer: Epidemiological Evidence, ... Epidemiological studies and large meta-analyses have consistently reported reduced CRC incidence and improved survival among patients with diabetes treated with ...

5. researchgate.net researchgate.net/publication/221971988_Metformin_efficacy_and_safety_for_colorectal_polyps_A_double-blind_randomized_controlled_trial

(PDF) Metformin efficacy and safety for colorectal polyps We devised a prospective randomized controlled trial to evaluate the chemopreventive effect of metformin against metachronous colorectal polyps ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3353167/

Metformin efficacy and safety for colorectal polyps We devised a prospective randomized controlled trial to evaluate the chemopreventive effect of metformin against metachronous colorectal polyps.

7. irjournal.org irjournal.org/journal/view.php?number=7

Does Metformin Affect The Incidence of Colonic Polyps and ... The Colorectal polyp detection rate was lower in the metformin group than in the non-meformin group (39.4% vs. 62.4%, P<0.01). Colorectal ...

8. tcr.amegroups.org tcr.amegroups.org/article/view/8671/html

Metformin: a promising candidate for chemoprevention of ... In a double blinded, randomized trial of 151 patients who underwent removal of colorectal polyps, use of metformin (250 mg per day) significantly reduced the ...