Myfortic for Type 1 Diabetes Islet Transplant Recipients

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Rodolfo Alejandro

Must be taking: Immunosuppressive medications

Disqualifiers: Hyperlipidemia, Obesity, Hypertension, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called Myfortic to assist individuals who have had islet transplants for type 1 diabetes but have lost transplant function. The focus is on determining if Myfortic can improve their condition by managing the immune system response. Individuals who have had at least one islet transplant and currently require immunosuppressive medication are suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity for participants to contribute to innovative research that could enhance transplant outcomes.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants may be on immunosuppressive medications or may need to stop them as per the current protocol of islet transplantation.

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

Research has shown that Myfortic has been studied in various contexts, including with kidney transplant patients. One study involving 423 kidney transplant recipients used Myfortic to help prevent organ rejection. These patients, aged 18 to 75, came from several countries, including the USA and Canada. This study provides insight into how well people tolerate Myfortic.

Generally, Myfortic is well-tolerated, but like any medication, it can cause side effects. Common side effects include stomach problems, headaches, and infections. Notably, the FDA has approved this medication for use in kidney transplant patients, indicating substantial safety information supports its use in this context.

This information may reassure potential trial participants about the safety of using Myfortic in new areas, such as islet transplantation for type 1 diabetes. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for Type 1 diabetes in islet transplant recipients, Myfortic offers a new approach by focusing on immune system modulation. Most current therapies aim to manage blood sugar levels or suppress the immune system broadly, but Myfortic specifically targets the immune pathways involved in transplant rejection. This precision could lead to fewer side effects and better outcomes for patients, making it an exciting option for researchers looking to improve transplant success rates.

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

Research has shown that Myfortic, which contains mycophenolic acid, plays a crucial role in transplants by preventing the immune system from attacking new cells. Previous studies have found that islet transplants in people with type 1 diabetes can lead to insulin independence, eliminating the need for insulin shots. In some cases, all patients became insulin independent, and many maintained this status for an extended period. This trial will evaluate Myfortic's role in supporting islet transplants, potentially improving blood sugar control and reducing episodes of low blood sugar in type 1 diabetes. ^{2 4 6 7 8}

Who Is on the Research Team?

Rodolfo Alejandro, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with Type 1 Diabetes who've had at least one islet transplant but now have complete graft loss. They must be on or able to stop immunosuppressants, mentally stable, and not pregnant or breastfeeding. Exclusions include a history of severe diseases like cancer (except certain skin cancers), heart disease, untreated high cholesterol, obesity, hypertension, liver issues, and active infections.

Inclusion Criteria

I have had at least one islet cell transplant.

Ability to provide written informed consent

I am not taking any immunosuppressive medications or have stopped them as required for islet transplantation.

Exclusion Criteria

You are currently using alcohol or drugs excessively.

Your liver function tests have shown consistently high levels, which means your liver may not be working properly.

You currently have an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Myfortic® monotherapy for 2 years following complete islet graft loss

104 weeks

Follow-up

Participants are monitored for sensitization using panel reactive antibody (PRA) levels after Myfortic® is weaned

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Myfortic

Trial Overview

The study tests Myfortic in individuals who have experienced complete loss of their transplanted islet cells after treatment for Type 1 Diabetes. It's an open-label trial where all participants receive the drug to see if it can prevent new immune sensitivities from developing post-graft rejection.

How Is the Trial Designed?

Group I: Myfortic treatment Experimental Treatment 1 Intervention

Treatment with Myfortic

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

Approved in United States as Myfortic for:

• Prevention of rejection in kidney transplant patients

Approved in European Union as Myfortic for:

• Prevention of rejection in kidney transplant patients

Who Is Running the Clinical Trial?

Rodolfo Alejandro

Lead Sponsor

Trials

10

Recruited

210+

Published Research Related to This Trial

This study analyzed the pharmacokinetics of mycophenolic acid (MPA) in 16 stable islet transplant recipients, revealing significant variability in drug absorption and metabolism, which is crucial for optimizing immunosuppressive therapy.

The pharmacokinetic parameters established, such as the area under the curve (AUC) and maximum concentration (Cmax), provide a foundational understanding for future research aimed at reducing variability in MPA dosing among islet transplant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of mycophenolic acid and its glucuronidated metabolites in stable islet transplant recipients. Al-Khatib, M., Shapiro, RJ., Partovi, N., et al.[2016]

In a study of 51 type 1 diabetic patients receiving islet transplants, the T cell-depleting immunosuppressive regimen was found to be safe, with no severe hypoglycemia or diabetic ketoacidosis reported in those with functioning grafts over a follow-up period of 48 months.

Older recipients (≥40 years) showed better graft function and longer benefits from the treatment without an increase in side effects, although 47% of patients experienced serious adverse events, including infections and cancer, which were mostly resolved with treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression. Lee, D., Keymeulen, B., Hilbrands, R., et al.[2018]

In a study of 8 Caucasian women undergoing islet cell transplantation, mycophenolic acid showed high variability in systemic exposure, indicating that individualized dosing and therapeutic monitoring may be essential for optimal treatment.

Despite some patients requiring dose reductions due to adverse effects, all participants achieved insulin independence, although 3 later experienced loss of graft function, highlighting the need for careful management of mycophenolic acid levels post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil in islet cell transplant: variable pharmacokinetics but good correlation between total and unbound concentrations. Jacobson, PA., Green, KG., Hering, BJ.[2016]

In a study of 65 Korean patients undergoing de novo renal transplantation, enteric-coated mycophenolate sodium (Myfortic) demonstrated a low incidence of biopsy-confirmed acute rejection at 10.8% within 6 months, indicating its efficacy in preventing rejection.

The safety profile showed that while 38.8% of patients experienced gastrointestinal discomfort, only 4.5% had reactions directly linked to the drug, and the overall patient and graft survival rates were high at 98.1% and 97.0%, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 6-month, open-label, multicenter clinical study in Korean de novo renal transplant patients evaluating the efficacy, safety, and tolerance of myfortic concomitantly used with tacrolimus. Ju, MK., Park, SH., Kim, SJ., et al.[2022]

A steroid-free maintenance immunosuppression protocol using mycophenolate mofetil (MMF) and cyclosporine (CSA) effectively maintained normoglycemia in non-human primate islet allograft recipients for 90 days, demonstrating its potential for improving islet transplantation outcomes.

Both auto-transplanted and immunosuppressed allograft recipients showed comparable beta cell function and insulin secretion, suggesting that this immunosuppression regimen can support islet function similarly to autografts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steroid-free maintenance of islet allografts using mycophenolate mofetil and cyclosporine in the non-human primate. Buss, J., Essig, E., Osei, K., et al.[2021]

In a study of 453 adult recipients of simultaneous pancreas-kidney transplants, those receiving a high dose of mycophenolate (1000 mg three times daily) showed significantly better pancreas allograft survival compared to those on a standard dose (1000 mg twice daily).

Despite the improved pancreas graft survival with high-dose mycophenolate, there were no significant differences in rejection rates, kidney graft survival, infection rates, or overall patient survival, indicating that the higher dose specifically benefits pancreas allograft outcomes without increasing other risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of intensive dosing of mycophenolate on pancreas allograft survival. Descourouez, JL., Jorgenson, MR., Menninga, N., et al.[2019]

Mycophenolic acid (MPA) has been shown to have a significant negative impact on pancreatic beta-cell viability and function, leading to increased apoptosis and reduced insulin secretion in both mouse and human islet cells.

The study found that MPA exposure resulted in altered islet architecture and down-regulation of key genes involved in beta-cell function, indicating its potential diabetogenic effects in the context of immunosuppressive therapy after organ transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro effects of mycophenolic acid on survival, function, and gene expression of pancreatic beta-cells. Gallo, R., Natale, M., Vendrame, F., et al.[2018]

Myfortic, an enteric coated formulation of mycophenolic acid (MPA), is designed to reduce gastrointestinal side effects compared to traditional MPA formulations.

This new formulation may improve patient tolerance and adherence to treatment by minimizing discomfort associated with gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myfortic (mycophenolate sodium) delayed-release tablets. Qureshi, A., Scheinfeld, N.[2017]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9767903/

Long-term Outcomes With Islet-Alone and Islet-After- ...

Insulin independence was achieved by 74% of islet-alone and islet-after-kidney transplantation recipients, with more than one-half maintaining insulin ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/20659093/

Islet transplantation in type 1 diabetics using an ... - PubMed

All patients achieved insulin independence and four out of eight patients became independent after single-islet transplants. Insulin independent patients had no ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S1600613522143765

Islet Transplantation in Type 1 Diabetics Using an ...

All patients achieved insulin independence and four out of eight patients became independent after single-islet transplants. Insulin independent patients had no ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT01909245

NCT01909245 | Islet Cell Transplant for Type 1 Diabetes

In previous research studies, islet transplantation has been successful in reducing low blood sugar episodes, improving overall blood sugar control, and in some ...

5.

openaccessjournals.com

openaccessjournals.com/articles/entericcoated-mycophenolate-mofetil-role-in-transplantation.pdf

Enteric-coated mycophenolate sodium: role in transplantation

This review outlines the mechanism of action of mycophenolic acid in transplantation. Its main side effects (gastrointestinal) often lead to dose reduction ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2009/050791s007lbl.pdf

Myfortic® - accessdata.fda.gov

The de novo study was conducted in 423 renal transplant patients (ages 18-75 years) in Austria, Canada,. Germany, Hungary, Italy, Norway, Spain, UK and USA.

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repository.niddk.nih.gov

repository.niddk.nih.gov/media/studies/cit-01/Protocol.pdf

CLINICAL ISLET TRANSPLANTATION (CIT) PROTOCOL CIT ...

The University of Minnesota has reported their preliminary experience with this regimen of ATG administration in 8 type 1 diabetic islet transplant recipients ( ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11140763/

Immunoprotection of cellular transplants for autoimmune type ...

In this review, we summarize the challenges with cellular immunological rejection and therapeutics used for islet transplantation.