Montbretin A for Type 2 Diabetes

(MbA Trial)

Recruiting at 1 trial location

Overseen By Michelle Storms

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Robert Petrella

Must not be taking: All medications

Disqualifiers: Poor health, Gastro-intestinal issues, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 2 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Montbretin A, a new treatment for type 2 diabetes, to determine its safety and whether it causes fewer side effects than other diabetes medications. Participants will take increasing doses while researchers monitor their blood sugar and heart activity. Individuals with type 2 diabetes managed by diet, or healthy individuals without diabetes who eat three regular meals a day, may qualify. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications to join the trial?

Yes, you must stop taking your current medications, except for vitamins and/or birth control, to participate in the trial.

Will I have to stop taking my current medications?

Yes, you will need to stop taking your current medications, except for vitamins and birth control, to participate in this trial.

Is there any evidence suggesting that Montbretin A is likely to be safe for humans?

Research shows that Montbretin A (MbA) is being developed as a treatment for diabetes. However, specific safety information for MbA in humans is not yet available. This trial is in its early stages and primarily focuses on safety, marking the first time the treatment is tested in people to assess their tolerance. Early trials like this typically use small doses and closely monitor participants for any side effects.

Montbretin A, derived from a plant, has shown promise in lab studies for aiding diabetes. While it appears hopeful, scientists are still gathering information. Participants in the trial will begin with small doses, which will gradually increase to ensure safety, with close monitoring for any negative effects.

Although solid safety data is not yet available, this approach demonstrates a careful and cautious method of testing Montbretin A in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for type 2 diabetes, which often include metformin, insulin, or sulfonylureas, Montbretin A (MbA) offers a fresh approach by potentially acting on different pathways. Researchers are excited about MbA because it is derived from a natural compound that might offer unique benefits, particularly in how it interacts with the body's glucose metabolism during meals. The treatment is administered in a controlled manner with standardized meals, possibly leading to more precise glucose control with fewer side effects. This new angle of targeting glucose levels in conjunction with meal intake presents a promising alternative to the current options.

What evidence suggests that Montbretin A might be an effective treatment for type 2 diabetes?

Research shows that Montbretin A (MbA), which participants in this trial will receive, could be a promising new treatment for type 2 diabetes. Derived from the montbretia plant, MbA is being developed to help control blood sugar levels. Early studies suggest that MbA might work by affecting certain processes involved in how the body handles sugar. Although limited data from human studies exist, the mechanism of MbA suggests it might have fewer side effects than current diabetes medications. This potential makes it an interesting option for future diabetes care. ^{1 2 3 4 6}

Who Is on the Research Team?

Robert Petrella, MD, PhD

Principal Investigator

University of British Columbia

Are You a Good Fit for This Trial?

This trial is for adults with type 2 diabetes who manage their condition through diet alone, have normal blood values, and eat three meals a day. Participants must use effective birth control or be sterile/menopausal. They should understand the study's schedule and medication dosing.

Inclusion Criteria

Normal dietary habit that includes three meals a day, as determined by the study doctor

Ability to return for all scheduled study visits

Ability to avoid all supplements that affect blood sugar for the duration of the study, including chromium, bitter melon, thiamine, berberine, alpha-lipoic acid, devil's claw, horse chestnut, fenugreek, ginseng, psyllium, cinnamon, garlic, and panax

Exclusion Criteria

Traveled to a foreign country less than four (4) weeks prior to study entry

Currently in poor health, as determined by the study doctor

I am taking medication other than vitamins or birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive increasing doses of Montbretin A (MbA) from 10 mg to 300 mg over a two-week period with a standardized meal

2 weeks

6 visits (in-person, 3 visits per week)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits scheduled one week and nine weeks after treatment completion

10 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Montbretin A

Trial Overview The Montbretin A (MbA) clinical trial tests the safety of MbA in treating type 2 diabetes and if it has fewer side effects compared to existing treatments. Patients will take increasing doses of MbA over two weeks alongside standardized meals.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

In this study, participants will receive increasing dosages of the Study Treatment (Montbretin A, MbA) at each treatment visit. The Study Treatment will be taken with a standardized meal (a meal that has specified quantities of carbohydrates, fats and proteins). At each visit, participants will receive one dose (in pill form) of MbA. As long as they are not experiencing any side effects, this dose will be gradually increased at each study visit (starting from 10 mg, 25 mg, 50 mg, 100 mg, 200 mg, to 300 mg MbA).

Montbretin A is already approved in Canada for the following indications:

Approved in Canada as Montbretin A for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Robert Petrella

Lead Sponsor

Trials

1

Recruited

50+

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Michael Smith Foundation for Health Research

Collaborator

Trials

20

Recruited

6,100+

Canadian Glycomics Network (GlycoNet) - Networks of Centres of Excellence (NCE)

Collaborator

Trials

1

Recruited

50+

Canadian Glycomics Network (GlycoNet)

Collaborator

Trials

2

Recruited

90+

Published Research Related to This Trial

Exenatide effectively improves glycemic control in patients with Type 2 diabetes by enhancing insulin secretion and suppressing appetite, leading to significant reductions in HbA1c and an average weight loss of 2 kg when used alongside metformin or sulfonylureas.

The treatment is generally well tolerated, with nausea being the most common side effect that decreases over time, and it poses a low risk of hypoglycemia, particularly when not combined with sulfonylureas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exenatide: incretin therapy for patients with Type 2 diabetes mellitus. Tahrani, AA., Piya, MK., Barnett, AH.[2019]

Incretin-based therapies, like exenatide, effectively manage Type 2 diabetes by enhancing insulin secretion in response to glucose, addressing key metabolic issues without a high risk of hypoglycemia.

Exenatide not only helps control blood sugar levels but also promotes weight loss and reduces caloric intake, making it a beneficial option for diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exenatide, a GLP-1 agonist in the treatment of Type 2 diabetes. Sennik, D., Ahmed, F., Russell-Jones, D.[2019]

A meta-analysis of 36 randomized trials involving GLP-1 receptor agonists for type 2 diabetes showed no significant increase in major cardiovascular events (MACE), with an overall odds ratio of 0.74, suggesting these medications are not harmful to heart health.

In placebo-controlled studies, GLP-1 receptor agonists demonstrated a significant reduction in MACE risk (odds ratio of 0.46), indicating potential cardiovascular safety, while results from active comparator studies showed no significant difference.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1 receptor agonists and cardiovascular events: a meta-analysis of randomized clinical trials. Monami, M., Cremasco, F., Lamanna, C., et al.[2021]

The U.S. FDA has approved six classes of oral medications for type 2 diabetes, with metformin and lifestyle changes recommended as the first-line treatments according to a consensus by the American Diabetes Association and the European Association for the Study of Diabetes.

New therapies in development, including incretin therapies and agents targeting metabolic syndrome, show promise for improving treatment options for type 2 diabetes, especially for patients struggling with weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes: new and future developments in treatment. Liao, EP.[2022]

Incretin-based therapies, including GLP-1 receptor agonists and DPP-4 inhibitors, effectively lower blood sugar levels in type 2 diabetes while also improving beta-cell function, blood pressure, and lipid levels, with a low risk of causing hypoglycemia.

GLP-1 receptor agonists are associated with weight loss, whereas DPP-4 inhibitors are weight neutral, highlighting important differences in their clinical profiles for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of incretin based therapies: clinical trial data. White, J.[2022]

Alogliptin, a selective dipeptidyl peptidase-4 inhibitor, has shown effectiveness and good tolerability in treating type 2 diabetes in Phase II and III studies, making it a promising option for patients.

This medication can be used alone or in combination with other diabetes treatments like metformin and insulin, and it has an excellent safety profile, addressing some of the limitations of current diabetes therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alogliptin: a novel molecule for improving glycemic control in type II diabetes mellitus. Ghatak, SB., Patel, DS., Shanker, N., et al.[2019]

Proactive intensification of insulin therapy in diabetes patients is crucial for minimizing the risks of chronic hypo/hyperglycemia and reducing weight gain while achieving personalized blood sugar targets.

This review provides evidence-based recommendations for physicians on how to effectively intensify insulin therapy and consider GLP-1 analogues for patients with type 2 diabetes who do not respond adequately to basal insulin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based recommendations for insulin intensification strategies after basal insulin in type 2 diabetes. Ghosh, S., Unnikrishnan, AG., Saboo, B., et al.[2018]

Intensive glucose control in type 2 diabetes can delay the onset and progression of both microvascular and possibly macrovascular diseases, highlighting the importance of early intervention and management strategies.

Combination therapy using insulin with oral medications like metformin can effectively normalize blood sugar levels while minimizing the need for intensive insulin regimens, although insulin therapy is associated with weight gain and hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin therapy in type 2 diabetes. Mudaliar, S., Edelman, SV.[2019]

In a study involving approximately 32,800 users of exenatide, there was a modestly higher incidence of claims for thyroid malignancies compared to users of metformin or glyburide, but this association was not significant when focusing on inpatient claims.

Exenatide use was not linked to an increased risk of benign thyroid neoplasms or pancreatic cancer, suggesting it may be a safe option regarding these specific cancer risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of health insurance claims for thyroid neoplasm and pancreatic malignancy in association with exenatide: signal refinement using active safety surveillance. Dore, DD., Seeger, JD., Chan, KA.[2021]

Incretin-based therapies, such as DPP-4 inhibitors and GLP-1 agonists, provide effective glycemic control for type 2 diabetes patients without the weight gain often seen with traditional treatments, making them a favorable option for many.

Clinical trial data suggest that these therapies are safe, showing no negative effects on cardiovascular health, and their integration into treatment plans can enhance options for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapeutic options: management strategies to optimize glycemic control. Freeman, JS.[2022]

Type 2 diabetes is primarily caused by issues with insulin resistance and declining beta-cell function, making it crucial for healthcare providers to understand these mechanisms to tailor effective treatments.

Newer treatments like incretin therapy fill a gap in diabetes management by modulating glucose supply, and combining different antidiabetic agents can significantly enhance glycemic control for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for the treatment of patients with type 2 diabetes mellitus: rationale and specific agents. Cefalu, WT.[2022]

Metformin is the first-line treatment for type 2 diabetes but often has limited efficacy over time, leading to the need for additional medications due to its gastrointestinal side effects and contraindications in certain patients.

Incretin-based therapies, particularly GLP-1 receptor agonists, are emerging as effective add-on treatments that can help achieve glycemic control while potentially offering cardiovascular benefits and improving β-cell function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological management of type 2 diabetes: the potential of incretin-based therapies. Charbonnel, B., Cariou, B.[2022]

Incretin-based therapies, such as GLP-1 receptor agonists and DPP-4 inhibitors, not only help control blood sugar levels in type 2 diabetes but also have weight-neutral or weight-reducing effects, making them beneficial for patients with obesity-related diabetes.

These therapies may preserve beta-cell function, suggesting they could modify the disease's progression, and early use of GLP-1 receptor agonists may prevent diabetes in at-risk individuals or slow down the disease in those already diagnosed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application of incretin-based therapy: therapeutic potential, patient selection and clinical use. Kendall, DM., Cuddihy, RM., Bergenstal, RM.[2022]

Incretin-based therapies, such as GLP-1 receptor agonists and DPP-4 inhibitors, not only help control blood sugar levels in type 2 diabetes but also have weight-neutral or weight-reducing effects, making them beneficial for patients with obesity-related diabetes.

These therapies may preserve beta-cell function, suggesting they could potentially modify the disease progression of type 2 diabetes, and early use might prevent diabetes in at-risk individuals or slow its progression in those already diagnosed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application of incretin-based therapy: therapeutic potential, patient selection and clinical use. Kendall, DM., Cuddihy, RM., Bergenstal, RM.[2011]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6899944/

Biosynthesis of the anti‐diabetic metabolite montbretin A Montbretin A (MbA) is a complex specialized metabolite found in the ornamental plant montbretia and being developed as a treatment for type 2 diabetes.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05826054

Montbretin Clinical Trial in Healthy Volunteers and Type 2 ... The goal of this clinical trial is to test the investigational product, Montbretin A (MbA) in either individuals with type 2 diabetes (T2D) or healthy ...

3. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/442216

Montbretin Clinical Trial in Healthy Volunteers and Type 2 ... The goal of this clinical trial is to test the investigational product, Montbretin A (MbA) in either individuals with type 2 diabetes (T2D) or healthy ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/tpj.16528

Improved production of the antidiabetic metabolite ... The plant-specialized metabolite montbretin A (MbA) is being developed as a new treatment option for type-2 diabetes, which is among the ten ...

5. withpower.com withpower.com/trial/phase-1-diabetes-mellitus-type-2-3-2023-f6bce

Montbretin A for Type 2 Diabetes (MbA Trial) This trial tests Montbretin A (MbA) in people with type 2 diabetes to see if it is safe and has fewer side effects than current treatments.

6. caymanchem.com caymanchem.com/product/30651/montbretin-a?srsltid=AfmBOopw8erhh7aN1gm_JI2-MbTSdjLAlNxmY3u0fPLcoS3nWTMPO7Cr

Montbretin A (MbA, CAS Number: 115712-92-0) Montbretin A is an acylated flavonol glycoside that has been found in C. crocosmiiflora and has antidiabetic activity. It inhibits human pancreatic α-amylase ...