DFMO for Type 1 Diabetes

(TADPOL Trial)

Recruiting at 6 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called DFMO (also known as Eflornithine) to determine if it can aid people with Type 1 Diabetes (T1D) by reducing stress on insulin-producing cells and preserving the body's insulin production. Participants will take either DFMO or a placebo, which resembles the drug but contains no active ingredients, twice daily for about six months. Ideal candidates are those diagnosed with T1D who began insulin treatment within the last 100 days. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that DFMO, the drug tested in this trial, has FDA approval for treating African Sleeping Sickness, indicating its safety for humans in that context. Other studies have generally found DFMO well-tolerated, with no widespread reports of serious side effects, meaning most people did not experience major negative effects.

In those studies, some people reported mild side effects, but they were not serious. Since this trial is in an early stage, it primarily assesses whether DFMO is safe and effective for people with Type 1 Diabetes. So far, earlier trials suggest it might help protect insulin-producing cells without causing serious safety issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Type 1 Diabetes?

Researchers are excited about DFMO for Type 1 Diabetes because it offers a novel approach by targeting the polyamine synthesis pathway. Unlike standard treatments like insulin therapy, which primarily manage blood sugar levels, DFMO could modify the disease process itself. This treatment uses difluoromethylornithine to inhibit an enzyme called ornithine decarboxylase, potentially reducing the autoimmune attack on insulin-producing cells. This unique mechanism could offer a new way to slow or even stop the progression of Type 1 Diabetes, providing hope for a more effective long-term solution.

What evidence suggests that DFMO might be an effective treatment for Type 1 Diabetes?

Research has shown that DFMO, which participants in this trial may receive, might help people with Type 1 Diabetes by protecting insulin-producing β cells. Studies have found that DFMO can help these cells continue functioning, potentially allowing the body to produce insulin for a longer time. DFMO is already used for other health issues, suggesting it could be safe and helpful for managing Type 1 Diabetes. Early findings indicate that DFMO is a promising option to help maintain insulin production and reduce stress on these important cells. ^{1 2 3 6 7}

Who Is on the Research Team?

Emily K Sims, MD,MS

Principal Investigator

Indiana University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10694631/

Inhibition of polyamine biosynthesis preserves β cell function ... These findings suggest that DFMO may preserve β cell function in T1D through islet cell-autonomous effects. Keywords: type 1 diabetes, islet, β ...

2. rileychildrens.org rileychildrens.org/research/featured-research/new-dfmo-drug-is-a-game-changer-for-patients-with-type-1-diabetes

New DFMO drug is a game changer for patients with type 1 ... The study's findings propose a novel approach to repurposing a-difluoromethylornithine (DFMO), an FDA-approved drug primarily used to treat African Sleeping ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05594563

TArgeting Type 1 Diabetes Using POLyamines (TADPOL) Clinical efficacy of 1000 mg/m2/day of oral DFMO after 3 months of treatment, 9 months after treatment (or 3 months after treatment end), and 12 months after ...

4. studyfinder.umn.edu studyfinder.umn.edu/studies/32451

TArgeting Type 1 Diabetes Using POLyamines (TADPOL) This study is looking at the safety and effects of Difluoromethylornithine (DFMO) and its effect on insulin production in people who have been newly diagnosed ...

5. medicine.iu.edu medicine.iu.edu/news/2023/10/type-1-diabetes-repurposed-drug-research

Repurposed drug offers new potential for managing type 1 ... The researchers' findings, published in Cell Reports Medicine, suggest repurposing of the drug α-difluoromethylornithine (DFMO) may open doors to innovative ...

6. studyfinder.umn.edu studyfinder.umn.edu/studies/32451.pdf

StudyFinder Study: 42022 Difluoromethylornithine (DFMO) to Preserve Insulin Production in Type 1 Diabetes ... Description: This study is looking at the safety and effects of ...

7. uchicagomedicine.org uchicagomedicine.org/find-a-clinical-trial/clinical-trial/irb230368

CLINICAL TRIAL / NCT05594563 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: