DFMO for Type 1 Diabetes

(TADPOL Trial)

Recruiting at 5 trial locations

Overseen By Operations Manager

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Emily K. Sims

Must not be taking: Steroids, Metformin, Antipsychotics, others

Disqualifiers: Diabetes other than T1D, Chronic illness, Psychiatric disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 6 months

70 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking medications that affect glucose metabolism, like steroids or metformin. It's best to discuss your current medications with the trial team.

How is the drug DFMO unique for treating type 1 diabetes?

DFMO (also known as Eflornithine) is unique because it is being explored as a potential treatment for type 1 diabetes, a condition that primarily relies on insulin therapy. Unlike traditional treatments, DFMO may offer a novel approach by targeting different pathways, although its exact mechanism in type 1 diabetes is still under investigation. ^{1 2 3 4 5}

What is the purpose of this trial?

The goal of this clinical trial is to test a drug known as DFMO in people with Type 1 Diabetes (T1D). The main question\[s\] it aims to answer are: * Does it reduce stress on the cells that make insulin? * Does it preserve what is left of the body's insulin production? Participants will take either DFMO or a placebo (looks like DFMO but has no active ingredients) two times a day for about 6 months. Participants will have 6 in person visits and 1 phone visit over a period of 12 months. Visits will include blood draws urine collection and other tests.

Research Team

Emily K Sims, MD,MS

Principal Investigator

Indiana University School of Medicine

Eligibility Criteria

The TADPOL trial is for people aged 6-40 with recent Type 1 Diabetes diagnosis, who still produce some insulin and have not used immunomodulatory drugs. They must have normal hearing, no psychiatric disorders affecting participation, and agree to use birth control if applicable. Excluded are those with conditions or medications influencing glucose metabolism, active seizure disorders, difficulty swallowing pills, certain blood or kidney issues.

Inclusion Criteria

Your hearing test results must show that you can hear quiet sounds at different pitches.

I am between 6 and 40 years old and have been diagnosed with Type 1 Diabetes.

I have not received any immune system modifying treatments.

Exclusion Criteria

I am not pregnant and agree to use two forms of birth control or remain abstinent.

I am allergic to milk or soy.

I am currently using anti-psychotic medication or have a psychiatric condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Eligibility is determined and glycemic control is optimized

Up to 45 days

Treatment

Participants receive either DFMO or placebo for 6 months

6 months

6 in-person visits, 1 phone visit

Wash-out

A 6-month period to assess the durability of the treatment effect

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• DFMO
• Placebo

Trial Overview This study tests DFMO's ability to reduce stress on insulin-producing cells and preserve insulin production in Type 1 Diabetes patients over a period of about six months. Participants will be randomly assigned to take either DFMO or a placebo twice daily and will undergo various tests including blood draws during their visits.

Participant Groups

Group I: Treatment Arm Active Control 1 Intervention

Difluoromethylornithine (DFMO) pill ,1000mg/m2/day, for 6 months

Group II: Placebo Arm Placebo Group 1 Intervention

Placebo pill taken twice a day orally for 6 months

DFMO is already approved in United States, European Union for the following indications:

Approved in United States as Eflornithine for:

• Sleeping sickness (African trypanosomiasis)
• Hirsutism

Approved in European Union as Eflornithine for:

• Sleeping sickness (African trypanosomiasis)

Who Is Running the Clinical Trial?

Emily K. Sims

Lead Sponsor

Trials

1

Recruited

70+

Juvenile Diabetes Research Foundation

Collaborator

Trials

237

Recruited

142,000+

Cancer Prevention Pharmaceuticals, Inc.

Industry Sponsor

Trials

8

Recruited

800+

Findings from Research

Sotagliflozin effectively lowers HbA1c levels in patients with type 1 diabetes mellitus (T1DM) without significantly increasing the risk of hypoglycemia, making it a promising option for better glycemic control.

However, the risk of diabetic ketoacidosis is notably higher with sotagliflozin, which means it should only be used in carefully selected patients who are well-informed and closely monitored by their healthcare provider.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An up-to-date evaluation of sotagliflozin for the treatment of type 1 diabetes. Chatzopoulos, G., Tziomalos, K.[2022]

In a study of 100 patients with type-1 diabetes and poor glycaemic control, metformin treatment for one year did not significantly improve HbA1c levels compared to placebo, indicating no enhancement in glycaemic control.

However, metformin was associated with a significant reduction in total daily insulin doses and body weight, suggesting potential benefits in insulin management and weight control for patients with type-1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study. Lund, SS., Tarnow, L., Astrup, AS., et al.[2022]

Treatment with AG490 in prediabetic NOD mice significantly delayed the onset of diabetes compared to control mice, indicating its potential efficacy in preventing Type 1 Diabetes (T1D).

AG490 not only enhanced regulatory T-cell functions and reduced blood glucose levels but also influenced the expression of PPARγ, suggesting that targeting the Jak-Stat signaling pathway could have both immunological and metabolic benefits in T1D prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyrphostin AG490 agent modestly but significantly prevents onset of type 1 in NOD mouse; implication of immunologic and metabolic effects of a Jak-Stat pathway inhibitor. Davoodi-Semiromi, A., Hassanzadeh, A., Wasserfall, CH., et al.[2021]

Dapagliflozin significantly reduces glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels in patients with type 1 diabetes, based on a meta-analysis of six randomized controlled trials involving various participants.

The treatment does not increase the risk of hypoglycemia or adverse events compared to placebo, but it is associated with a higher incidence of ketone-related events, indicating a need for monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of dapagliflozin for type 1 diabetes: a meta-analysis of randomized controlled studies. Ma, J., Zhao, Y., Fan, H., et al.[2022]

Insulin analogues are crucial for managing type 1 diabetes as they provide dynamic action profiles that mimic natural insulin release, allowing for better glycaemic control with a lower risk of hypoglycaemia compared to traditional human insulins.

The review highlights the importance of both patient education and the development of insulin preparations that offer stable basal coverage and appropriate mealtime peaks, which are essential for helping individuals with type 1 diabetes lead active lives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin analogues in type 1 diabetes mellitus: getting better all the time. Mathieu, C., Gillard, P., Benhalima, K.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

An up-to-date evaluation of sotagliflozin for the treatment of type 1 diabetes. [2022]

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

Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Tyrphostin AG490 agent modestly but significantly prevents onset of type 1 in NOD mouse; implication of immunologic and metabolic effects of a Jak-Stat pathway inhibitor. [2021]

4. Uganda pubmed.ncbi.nlm.nih.gov

The efficacy of dapagliflozin for type 1 diabetes: a meta-analysis of randomized controlled studies. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Insulin analogues in type 1 diabetes mellitus: getting better all the time. [2022]