Curing Diabetes

1. What are islet cells?

The Islets of Langerhans in the pancreas are commonly referred to as “islets” (pronounced “EYE-lets”) constitute what is known as the endocrine pancreas. Islets actually are clusters of cells, with each “islet” containing 3,000 to 4,000 cells. Scientists estimate there are 0.5 – 1 million islets of different shapes and sizes scattered throughout a healthy adult pancreas. They make up only one to two percent of the entire organ. Although insulin-producing islet cells cease to function in people with type 1 diabetes, the remaining 98 percent of the pancreas (exocrine pancreas) continues to function normally, producing digestive enzymes.

2. What is islet transplantation?

In this procedure, researchers isolate the islets from the rest of the donor pancreas and transplant them into patients with diabetes. Traditionally, islets have been infused into the recipient’s liver. While DRI researchers have shown that transplanted islets can function in patients for more than a decade – with some patients living without the need for insulin therapy – the liver is not an optimal site for many reasons. Armed with observations and data from decades of experience in clinical islet transplantation, DRI researchers are working to overcome the challenges associated with this cell replacement therapy.

3. Has islet transplant in the eye been done before in humans?

No, islet transplant in the eye has not been done before in humans. But DRI researchers have been transplanting islets into study models for more than ten (10) years. This Phase I/II clinical trial, which is done in collaboration with the Bascom Palmer Eye Institute, represents the first stage in testing the eye as an alternative site to the liver in housing transplanted islet cells.

4. What are the criteria for this pilot trial?

Some of the initial criteria for participating in this trial include:
– Age 18 – 70 years
– More than 5 years with type 1 diabetes (diagnosed <40 years of age)
– Legal blindness in one (1) or both eyes
– Have stable kidney function of native or transplanted kidney

Additional inclusion and exclusion criteria will be reviewed during the screening process.

5. Will islet transplant in my eye affect my vision?

We do not know. However, eligible participants in this trial must be legally blind in the eye where the islets will be transplanted. In this initial trial, we hope to learn if transplanting islets in the eye is safe and can improve blood sugar control in diabetic patients.

6. Will anti-rejection drugs be needed in this trial?

Yes. While some eligible participants in this trial will be already on maintenance immunosuppression for their kidney transplant, they will receive a short induction of immunosuppression in the days around the islet transplant in the eye. Eligible participants without a kidney transplant will receive the same induction therapy and maintenance immunosuppression for two (2) years after the transplant.

7. Does transplanting islets in the eye offer an advantage to reducing immunosuppression?

This protocol will use induction immunosuppression in the days around the islet transplant in the eye and maintenance immunosuppression for two (2) years after the transplant. Participants with a kidney transplant will receive only induction immunosuppression without interferinge with the existing maintenance immunosuppression for the kidney transplant. However, we believe the eye can confer some benefits that favor long term islet survival and, if we can demonstrate this concretely and over time, we may be able to reduce the anti-rejection drugs.

8. Will everyone who participates be given the same treatment or will a placebo be involved?

Each person selected for participation will receive the same treatment as indicated in the approved protocol. Organ and tissue transplantation studies do not use placebo procedures in their testing of a new treatment. They do compare the current trial results with other previously conducted trial protocols to determine the effects of a new therapy/site.

9. How many patients will participate in this clinical trial?

Pilot trials are designed to be the first step in the clinical research process and provide important data for larger studies. The FDA (Food and Drug Administration) has approved this pilot trial for ten (10) participants.

10. If I participated in a previous trial, would I be eligible for this pilot trial?

It depends on what type of trial you participated in and how long before enrolling in this trial. Individuals who previously received an islet transplant will not be eligible for this initial pilot trial. Individuals who previously received a pancreas transplant will not be eligible for this trial unless the transplanted pancreas failed within the first two (2) weeks due to thrombosis. If you used any investigational drug/agent within four (4) weeks from enrolling in this trial, you will not be eligible. If you participated in any other clinical trial, please call the DRI’s Clinical Cell Transplant Program at 305-243-5321 to discuss your eligibility.

11. If I submitted a screening application in the past, am I already among the pool to be considered for islet transplantation pilot trials?

If you have been identified as an eligible candidate for islet transplantation within the past year, you should contact the DRI’s Clinical Cell Transplant Program at 305-243-5321 to confirm your interest and ask if additional information is needed to update your application. If it has been more than a year, you will need to resubmit the application with current information.

12. After submitting the application, how long will it take for me to learn whether or not I am eligible to participate in this pilot clinical trial?

A member of the DRI’s Clinical Cell Transplant Program will be notifying you of your status within two (2) weeks of your application submission. Each applicant will be contacted individually by phone, mail or email. Based on the information in your initial application expressing your interest in participating in this trial, a phone interview may be set up to conduct an initial screening to evaluate your eligibility. If you meet the initial screening criteria, you may be invited to the DRI and/or BPEI to complete the screening process by undergoing a battery of tests to determine your eligibility and whether you can be included as a participant on the active waiting list.

13. How much does it cost to participate in this trial?

You will likely have expenses to participate in this trial that may or may not be covered by your insurance. You will not be paid for being in this research study. After meeting the initial screening criteria and being selected for participation in this clinical trial, you may have expenses associated with travel to and from the clinic/hospital where screening for this study. Patients will be responsible for travel and housing costs for their initial screening process. You and your insurance carrier will be responsible for paying for any laboratory studies considered to be regular medical care for your diabetes, kidney transplant (if you have one), eye care, or other medical conditions, even though these tests may also be required by the research protocol. The study will only cover insurance co-pays for research-only tests during the screening to evaluate your eligibility. The study will also pay for all costs related to the transplant procedure and medications as well as study-related follow up visits.

14. If I meet the criteria to participate in the pilot trial and am placed on the waiting list, how do the DRI and BPEI researchers select who on this list gets the transplant?

The selection of individuals from the active waiting list to receive islets is based on several factors including, but not limited to, donor-recipient tissue compatibility (commonly referred to as “matching”), time on the waiting list, and obtaining healthy islets from a donor organ through UNOS. The more candidates are on the active waiting list, the better the chance for a suitable “match.”

15. Will this clinical pilot trial be open to children?

No. see question 4 above for age and other restrictions. Also see study NCT02846571 at ClinicalTrials.gov for more information on the inclusion/exclusion criteria of this trial.

16. What are the next steps after this pilot trial?

If we can demonstrate the primary safety and efficacy criteria of this trial, we will seek FDA approval to increase the number of participants. If safety and efficacy are demonstrated in larger cohorts, future trials will evaluate the safety of transplanting islets in seeing eyes. Consistent with our efforts at the DRI to reduce or eliminate immunosuppression, other future trials will also evaluate the benefits of local immunosuppression applied directly to the eye where the islets are transplanted as well as the potential of resetting/training the immune system to avoid immune attack against the transplanted islets. DRI scientists and collaborators are developing and testing approaches for therapeutic options to reset/train the immune system and establish immune tolerance to accept the new, healthy islets, as well as prevent the recurrence of the autoimmune process that caused diabetes in the first place. If successful, life-long immunotherapy would not be needed.