Anti-Inflammatory Therapy for Chronic Pancreatitis

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Minnesota

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

Disqualifiers: Diabetes, HIV, Hepatitis, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for individuals with severe chronic pancreatitis undergoing TPIAT, a procedure where the pancreas is removed and islets are transplanted to reduce diabetes risk. The study aims to determine if two anti-inflammatory treatments, etanercept (a medication that reduces inflammation) and alpha-1 antitrypsin (a protein that protects tissues from inflammation), can better protect transplanted islets compared to standard care. Participants will be randomly assigned to receive one of these treatments or standard care to evaluate which approach best maintains long-term insulin independence. Suitable candidates for this trial are those planning to undergo TPIAT at the University of Minnesota without a pre-existing diabetes diagnosis. As a Phase 4 trial, this research involves treatments already FDA-approved and proven effective, aiming to understand how they can benefit more patients.

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-related drugs, at least 30 days before enrolling. If you are currently using corticosteroids or any medication that affects glucose tolerance, you may also need to stop those, unless it's a specific type like hydrocortisone for replacement or topical forms.

What is the safety track record for these treatments?

Research has shown that both etanercept and alpha-1 antitrypsin (A1AT) are generally safe for humans, which is promising for their use in treating chronic pancreatitis patients undergoing TPIAT.

Etanercept is already available for other conditions and is usually safe to use. However, some studies have reported serious but non-life-threatening side effects in certain groups. While etanercept is mostly well-tolerated, monitoring for any side effects remains important.

For alpha-1 antitrypsin, research indicates it is safe, with no major differences in side effects compared to standard treatments. Studies on patients with various conditions have shown that A1AT is generally well-tolerated.

Both treatments have demonstrated potential to protect transplanted islets, which could lead to better outcomes for those undergoing TPIAT. Overall, the safety of these treatments makes them strong candidates for further study in this clinical trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for chronic pancreatitis because they offer novel approaches to reducing inflammation, a key issue in this condition. Unlike traditional treatments such as pain management and enzyme supplements, etanercept works by inhibiting tumor necrosis factor (TNF), a protein that fuels inflammation, potentially offering more targeted relief. Alpha 1-Antitrypsin, on the other hand, may reduce inflammation by protecting tissues from enzymes that cause damage. These innovative mechanisms provide hope for more effective management of symptoms and improved quality of life for patients.

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

Research has shown that etanercept, one of the treatments in this trial, blocks a specific protein involved in inflammation and may enhance the survival of transplanted islet cells. In one study, 75% of patients who received etanercept stopped using insulin long-term, indicating it helps protect transplanted cells soon after surgery. Meanwhile, alpha-1 antitrypsin (A1AT), another treatment option in this trial, reduces inflammation and protects insulin-producing cells. Although A1AT has not shown significant improvement in some measures of insulin production in certain studies, it has effectively extended the survival of transplanted cells in animal studies. Both treatments aim to improve outcomes for individuals undergoing total pancreatectomy with islet autotransplantation (TPIAT) by reducing inflammation and protecting transplanted cells. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

Adults aged 18-68 with severe chronic pancreatitis, scheduled for a pancreas removal and islet transplant at the University of Minnesota, can join. They must be able to consent and not have conditions like IgA deficiency, HIV, hepatitis B/C, TB, certain blood disorders or use medications affecting glucose tolerance. Pregnant women or those planning pregnancy are excluded.

Inclusion Criteria

Able to provide informed consent

I am approved for a complete pancreas removal and islet auto-transplant at UM.

Exclusion Criteria

I have diabetes or my blood sugar or A1c levels are high.

Known hypersensitivity to specific medications

I haven't used specific treatments in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either etanercept or alpha-1 antitrypsin in addition to standard TPIAT procedure

4 weeks

Multiple visits for drug administration and assessments

Early Post-operative Monitoring

Mechanistic assessments including inflammatory cytokines and chemokines and measures of beta cell loss

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including metabolic testing at 90, 365, and 730 days post-TPIAT

2 years

Periodic visits for metabolic testing

What Are the Treatments Tested in This Trial?

Interventions

• Alpha 1-Antitrypsin
• etanercept

Trial Overview The trial tests if anti-inflammatory drugs etanercept or alpha-1 antitrypsin improve outcomes after total pancreatectomy with islet autotransplant (TPIAT). Participants will either receive one of these drugs or standard care post-surgery and will be monitored for up to two years.

How Is the Trial Designed?

Group I: etanercept Experimental Treatment 1 Intervention

Patients in the etanercept arm will undergo the usual procedure of TPIAT with additional therapy of etanercept.

Group II: alpha-1 antitrypsin Experimental Treatment 1 Intervention

Patients in the alpha-1 antitrypsin arm will undergo the usual procedure of TPIAT with additional therapy of alpha-1 antitrypsin (Aralast NP)

Group III: Standard Care Active Control 1 Intervention

Patients in the standard care arm will undergo the usual procedure of TPIAT with no ancillary therapies provided.

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11044796/

Alpha-1 Antitrypsin Augmentation Therapy in Chronic ... In this prospective, randomized, double-blind clinical trial, we evaluated the safety and efficacy of 60 mg/kg human alpha-1 antitrypsin (AAT) or placebo ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38659255/

Alpha-1 Antitrypsin Augmentation Therapy in Chronic ... Although AAT therapy did not show improvement in C-peptide AUC in this study, AAT therapy is safe in CP patients and there are experiences gained on optimal ...

3. fda.gov fda.gov/media/73793/download

Alpha 1 Proteinase Inhibitor (Human) Aralast Package Insert Clinical data demonstrating the long–term effects of chronic augmentation or replacement therapy of individuals with. Aralast are not available. Safety and ...

4. fda.gov fda.gov/media/69965/download

Package Insert - Aralast NP Clinical data demonstrating the long-term effects of chronic augmentation and maintenance therapy with. ARALAST NP or ARALAST are not available. ARALAST NP is ...

5. researchgate.net researchgate.net/publication/371749424_839-P_Alpha-1_Antitrypsin_Augmentation_Therapy_in_Chronic_Pancreatitis_Patients_Undergoing_Total_Pancreatectomy_and_Islet_Autotransplantation

839-P: Alpha-1 Antitrypsin Augmentation Therapy in ... The primary efficacy outcome was not significantly different between groups. Baseline characteristics including age, body weight, BMI, HbA1C, etc, were ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7886062/

Alpha-1 antitrypsin deficiency: an update on clinical ... Primary outcome: the safety of alpha-1 proteinase inhibitor evaluated by the proportion of subjects experiencing AEs, SAEs, and AEs leading ...

7. aetna.com aetna.com/cpb/medical/data/100_199/0145.html

Alpha1-Proteinase Inhibitors - Medical Clinical Policy ... These researchers studied the safety and pharmacokinetics of Aralast NP (AAT). This open-label, dose-escalation study enrolled 8 adults aged 16 to 35 years ...