Islet Transplant Techniques for Chronic Pancreatitis

(iSite Trial)

Overseen By Kristine Mulier

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Must not be taking: Insulin, Metformin, Corticosteroids, others

Disqualifiers: Diabetes, Liver disease, Coagulopathy, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to treat chronic pancreatitis by testing two methods of islet transplantation. One group receives only intrahepatic islets (placed in the liver), while the other group receives a portion of their islets in an omental pouch (a fold in the abdomen), in addition to intrahepatic placement. The researchers aim to assess how these methods impact islet function, which can affect insulin production and help manage chronic pancreatitis symptoms. Individuals scheduled for total pancreatectomy and islet autotransplantation at the University of Minnesota might be suitable candidates for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research in islet transplantation methods.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, such as insulin, metformin, and other diabetes treatments, at least 30 days before joining. You also cannot use corticosteroids or any medication that affects glucose tolerance, except for specific types like topical or inhaled glucocorticoids.

What prior data suggests that these islet transplant techniques are safe?

Research shows that the omental pouch technique for islet transplantation might be a safe option. In studies, this method has shown promise in managing diabetes by helping control blood sugar levels. Previous findings suggest that this approach may improve quality of life by reducing pain after pancreas removal. However, more research is needed to fully understand its safety and effectiveness in humans.

Intrahepatic islet transplantation, where islets are placed in the liver, has been a well-established method for helping those with insulin-dependent diabetes. This technique is generally well-tolerated and has a good safety record.

These findings suggest safety, but more research is ongoing to confirm these results. Prospective participants should discuss potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about islet transplant techniques for chronic pancreatitis because they offer a unique approach to managing this painful condition. Unlike traditional treatments that focus on managing pain or enzyme supplementation, these techniques aim to restore insulin production by transplanting islets either into the liver (intrahepatic) or a new site called the omental pouch. This could potentially eliminate the need for lifelong insulin therapy. The new delivery method using the omental pouch is particularly intriguing, as it might provide a more favorable environment for the islets to function effectively, potentially improving outcomes for patients.

What evidence suggests that this trial's treatments could be effective for chronic pancreatitis?

Research has shown that islet autotransplantation, which involves relocating insulin-producing cells within the body, can benefit people with chronic pancreatitis. In this trial, participants will receive either intrahepatic islets alone or a combination of intrahepatic islets and islets in the omental pouch. One study found that placing these cells in the omental pouch, a fold of tissue in the abdomen, helped achieve normal blood sugar levels and reduced the need for insulin. Another report showed that 90% of patients who had their pancreas removed and received this cell transplant rated their outcomes as good to excellent. Additionally, using the omental pouch for this procedure is considered a safe and effective option. These findings suggest promising results for managing chronic pancreatitis with this method. ^{1 4 5 6 7}

Who Is on the Research Team?

Greg Beilman, MD

Principal Investigator

University of Minnesota, Department of Surgery

Are You a Good Fit for This Trial?

This trial is for adults aged 18-68 who are scheduled for total pancreatectomy and Islet AutoTransplant at the University of Minnesota, without pre-existing diabetes or certain blood sugar levels. They must be able to consent and not have used specific diabetes treatments recently, steroids that affect glucose tolerance, or have severe anemia, low platelets/neutrophils.

Inclusion Criteria

I am approved for a total pancreatectomy and islet autotransplantation at the University of Minnesota.

Able to provide informed consent

Exclusion Criteria

My liver enzymes are higher than normal, but it's not due to a benign condition like Gilbert's.

Any of the following hematologic abnormalities: server anemia (hemoglobin <10 g/dL), thrombocytopenia (<150/mm3), or neutropenia(<1.0 x 109/L).

Any other medical condition that , in the opinion of the investigator, may interfere wit the patient's ability to successfully and safely complete the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Islet Transplantation

Participants undergo total pancreatectomy and islet autotransplantation, with randomization to intra-portal alone or intra- and extra-portal transplantation

Immediate post-operative period

Inpatient stay for surgery and recovery

Post-operative Monitoring

Participants are monitored for surgical complications and portal vein thrombosis using abdominal ultrasound

4-5 days

Daily inpatient monitoring

Follow-up

Participants are monitored for safety and effectiveness, including glucose monitoring and hypoglycemic episodes

1 year

Regular outpatient visits and continuous glucose monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Intrahepatic islets alone
• Intrahepatic islets and islets in the omental pouch

Trial Overview The study tests two methods of pancreatic islet transplantation in patients undergoing surgery for chronic pancreatitis: one group receives islets into their liver (intrahepatic) and another group gets them both in the liver and an omental pouch. A control group of normal volunteers will help compare outcomes related to islet function.

How Is the Trial Designed?

Group I: Intrahepatic and omental pouch islets Experimental Treatment 1 Intervention

Group II: Intrahepatic islets alone Active Control 1 Intervention

Group III: Normal Volunteers Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6180729/

Omental Pouch Technique for Combined Site Islet ... The omental pouch technique may represent a safe and effective alternate site for islet autotransplantation. Further study is needed to confirm these findings.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666379123000514

Bioengineered omental transplant site promotes pancreatic ... Herein, we demonstrate that full euglycemia and insulin independence are achieved by transplanting islets to the omentum in a one donor-one ...

3. academic.oup.com academic.oup.com/edrv/article/40/2/631/5239681

Pancreatic Islet Transplantation in Humans - Oxford Academic Overall results of TPIAT were judged as good to excellent by 90% of recipients, fair by 8%, and poor by 2% (29). In another series of 85 consecutive patients ...

4. nature.com nature.com/articles/s43856-022-00087-7

Quality of life and metabolic outcomes after total ... Introduction. Traditionally, islet autotransplantation (IAT) has been performed in patients undergoing pancreatectomy for chronic pancreatitis.

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03779139/intra-portal-alone-versus-intra-and-extra-portal-transplantation-of-pancreatic-islets-after-total-pancreatectomy-for-chronic-pancreatitis?mp=amf&page=56&state=MN&city=Minneapolis

and Extra-Portal Transplantation of Pancreatic Islets After ... More than 90% of patients with chronic pancreatitis have been hospitalized, half use narcotic analgesics regularly, and one-fourth are on ...

6. ccjm.org ccjm.org/content/83/6/435

Total pancreatectomy and islet cell autotransplantation Total pancreatectomy and islet cell autotransplant controls pain and improves quality of life while often minimizing the development of overt diabetes.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8528405/

An overview of current advancements in pancreatic islet ... Isografts of rat islets transplanted into the omentum pouch resulted in normoglycemia in insulin-dependent diabetic rats, and the removal of the pouch ...