Proglumide for Chronic Pancreatitis

(ProCP Trial)

Overseen By Victor Ciofoaia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Georgetown University

Disqualifiers: Alcohol abuse, Renal insufficiency, Cirrhosis, others

Compensation: Varies

Number of Visits: 11

32 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests proglumide, an older drug, to see if it can help people with chronic pancreatitis by blocking a protein that causes inflammation and pain. The study targets patients with severe symptoms and aims to reduce their pain and improve pancreatic function.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have stable doses of anti-diabetic medication for at least 90 days before screening, which suggests you may continue those medications.

What data supports the effectiveness of the drug Proglumide for chronic pancreatitis?

Research on rats with acute pancreatitis showed that Proglumide, a drug that blocks certain digestive hormones, led to some biochemical changes suggesting potential benefits, but it did not improve survival rates. This suggests that while Proglumide might have some effects on pancreatic enzymes, it may not be effective as a sole treatment for pancreatitis. ^{1 2 3 4 5}

Is proglumide safe for use in humans?

Proglumide has been tested in rats for pancreatitis, showing some biochemical changes but not improving survival rates, and higher doses even reduced survival. This suggests caution in its use, and it may not be safe as the sole treatment for pancreatitis. ^{1 3 6 7 8}

How does the drug Proglumide differ from other treatments for chronic pancreatitis?

Proglumide is unique because it works by blocking cholecystokinin (CCK) receptors, which may help reduce certain enzyme levels in the pancreas. However, it has not shown improved survival rates in acute pancreatitis, suggesting it may not be effective as a sole treatment. ^{1 3 6 9 10}

Research Team

Jill P Smith, MD

Principal Investigator

Georgetown University

Eligibility Criteria

Adults aged 18-75 with confirmed chronic pancreatitis who experience significant pain despite medication can join. They must have stable diabetes treatment if applicable and agree to use contraception. Excluded are those with kidney issues, liver disease, anemia, gallbladder problems, type 1 diabetes, or substance abuse.

Inclusion Criteria

My pain is not well-managed with my current medications.

I have ongoing symptoms of pancreatitis.

My diabetes medication dose has been the same for the last 3 months.

Exclusion Criteria

Liver enzymes > 2x ULN, Hgb <8.5, Creat>2; HgbA1c>8

I have Type 1 Diabetes.

Currently abusing alcohol (more than three drinks in a day or more than seven drinks per week) or nonprescription drugs

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Observation

Baseline pain surveys and diaries are completed to establish pain levels

4 weeks

1 visit (in-person or virtual)

Treatment Part 1

Open-label treatment with proglumide for 12 weeks

12 weeks

4 visits (in-person)

Treatment Part 2

Randomized placebo-controlled pseudo-crossover study with proglumide or placebo

24 weeks

4 visits (in-person)

Follow-up

Safety check and assessment of symptoms after treatment completion

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Placebo
• Proglumide

Trial Overview The trial is testing Proglumide's safety and its ability to reduce pain and improve pancreatic function in chronic pancreatitis patients. It includes an initial open-label phase for eight subjects followed by a randomized double-blind phase with placebo and Proglumide treatments.

Participant Groups

Group I: Proglumide Experimental Treatment 1 Intervention

Proglumide therapy 400 mg by mouth three times daily for 12 weeks in a blinded fashion followed by continued proglumide 400 mg by mouth three times daily for 12 additional weeks in an open labeled fashion. Hence this arm receives proglumide for a total of 24 weeks.

Group II: Placebo Placebo Group 1 Intervention

Arm 1. Placebo for first 12 weeks. Placebo is a fiber filler called Avicel and is given by mouth three times daily. Note: After 12 weeks on placebo, these subjects will receive proglumide 400 mg orally three times daily open labeled for 12 additional weeks.

Who Is Running the Clinical Trial?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

Findings from Research

In a study involving 6,005 patients with type 2 diabetes, dulaglutide was associated with a low incidence of acute pancreatitis, with only 3 confirmed cases among those treated, which is comparable to the placebo group.

The exposure-adjusted incidence rate of acute pancreatitis was 0.85 patients per 1,000 patient-years for dulaglutide, significantly lower than the rates for placebo (3.52) and sitagliptin (4.71), suggesting that dulaglutide has a favorable safety profile regarding pancreatitis risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Pancreas Safety in the Development Program of Once-Weekly GLP-1 Receptor Agonist Dulaglutide. Nauck, MA., Frossard, JL., Barkin, JS., et al.[2018]

In a study involving liraglutide users followed for a median of 15 months, the incidence rate of acute pancreatitis was slightly higher (187.5 cases per 100,000 person-years) compared to other non-GLP-1 therapies, but this difference was not statistically significant (adjusted RR 1.10).

For pancreatic cancer, liraglutide showed a lower incidence rate (19.9 cases per 100,000 person-years) compared to non-GLP-1 therapies (33.0 cases), suggesting no increased risk associated with liraglutide (adjusted RR 0.65).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, claims-based assessment of the risk of pancreatitis and pancreatic cancer with liraglutide compared to other antidiabetic drugs. Funch, D., Gydesen, H., Tornøe, K., et al.[2021]

Data from the FDA Adverse Event Reporting System suggest that incretin-based therapies, like GLP-1 receptor agonists and DPP-4 inhibitors, may increase the risk of acute pancreatitis and pancreatic cancer.

However, population-based observational studies do not support these findings, indicating that current evidence is conflicting and insufficient to determine the true risk associated with these diabetes treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incretin-mimetic therapies and pancreatic disease: a review of observational data. Suarez, EA., Koro, CE., Christian, JB., et al.[2022]

The new pancreatine formulation, Panzytrat, significantly improves the duration and quality of life for patients, especially children, suffering from chronic pancreatitis and cystic fibrosis, as shown in clinical studies involving 4,557 participants.

Panzytrat has demonstrated high efficacy and safety in both open and double-blind comparative clinical studies, making it a suitable treatment for various pancreatic excretory insufficiency symptoms, including those following surgeries or oncological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of Panzytrat in the replacement therapy of exocrine pancreatic insufficiency (an analytical review)]. Karamysheva, EI., Lobanova, EG.[2007]

References

1. United States pubmed.ncbi.nlm.nih.gov

Assessment of Pancreas Safety in the Development Program of Once-Weekly GLP-1 Receptor Agonist Dulaglutide. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Pancreatic function, quality of life and costs at long-term follow-up after acute pancreatitis. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Proglumide treatment in bile-induced acute experimental pancreatitis. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Incretin-based therapy and risk of acute pancreatitis: a nationwide population-based case-control study. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Chronic pancreatitis. The problems of diagnostic criteria. [2006]

6. United States pubmed.ncbi.nlm.nih.gov

PANCREATIC SAFETY IN STUDIES OF THE GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST ALBIGLUTIDE. [2021]

7. England pubmed.ncbi.nlm.nih.gov

A prospective, claims-based assessment of the risk of pancreatitis and pancreatic cancer with liraglutide compared to other antidiabetic drugs. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Incretin-mimetic therapies and pancreatic disease: a review of observational data. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

An Investigative Study of Pancreatic Exocrine Biomarkers, Histology, and Histomorphometry in Male Zucker Diabetic Fatty (ZDF) Rats Given Dulaglutide by Subcutaneous Injection Twice Weekly for 13 Weeks. [2022]

10. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Use of Panzytrat in the replacement therapy of exocrine pancreatic insufficiency (an analytical review)]. [2007]