Proglumide for Chronic Pancreatitis

(ProCP Trial)

Not currently recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests proglumide, an older drug, to determine its potential benefits for people with chronic pancreatitis, a condition that causes severe abdominal pain, diarrhea, and an increased risk of pancreatic cancer. Researchers aim to discover if proglumide can alleviate pain and improve pancreatic function by blocking a protein associated with inflammation and damage. The study consists of two parts: one group starts with a placebo (a fake treatment) and later switches to proglumide, while another group takes proglumide from the start. Individuals with chronic pancreatitis, whose pain is not controlled by medication, might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, the study focuses on understanding how proglumide works in people and measuring its effectiveness in an initial group, offering participants a chance to contribute to important research.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that proglumide is generally safe and well-tolerated for people with chronic pancreatitis. Studies have found that a daily dose of 1200 mg is safe for most patients. This treatment aims to relieve pain and may also address scar tissue build-up in the pancreas. While proglumide appears promising, it is important to note that the data comes from trials with specific doses. The current study continues to gather more information on its safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic pancreatitis?

Proglumide is unique because, unlike traditional treatments for chronic pancreatitis that primarily focus on pain management and enzyme supplements, it targets the underlying inflammation and pain pathways. Most treatments for this condition rely on managing symptoms, but Proglumide is believed to block specific receptors involved in pain transmission, potentially offering more comprehensive relief. Researchers are excited because this new mechanism of action could lead to more effective and prolonged symptom control for patients.

What evidence suggests that proglumide might be an effective treatment for chronic pancreatitis?

Research has shown that proglumide might help treat chronic pancreatitis by blocking a specific receptor linked to inflammation and scarring in the pancreas. In animal studies, proglumide reduced thickening, scarring, and inflammation of the pancreas. Some studies also suggest that proglumide could help reduce pain in people with chronic pancreatitis. These effects make it a promising option for relieving symptoms and possibly slowing the disease's progression. While more research is needed, early findings are hopeful. Participants in this trial will receive either proglumide or a placebo to further evaluate its effectiveness. ^{1 2 3 4 5}

Who Is on the Research Team?

Jill P Smith, MD

Principal Investigator

Georgetown University

Are You a Good Fit for This Trial?

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.

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

I have ongoing symptoms of pancreatitis.

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38794273/

The Role of a Cholecystokinin Receptor Antagonist ... - PubMed We conclude that proglumide is safe and well tolerated in most subjects with CP at a dose of 1200 mg per day. Furthermore, proglumide therapy ...

2. mdpi.com mdpi.com/1999-4923/16/5/611

The Role of a Cholecystokinin Receptor Antagonist in ... In animal models of chronic pancreatitis, we found that proglumide decreased pancreatic fibrosis and inflammation [16]. Proglumide also decreased the formation ...

3. mission-cure.org mission-cure.org/new-clinical-trial-testing-a-repurposing-drug-proglumide-aims-to-treat-pain-in-chronic-pancreatitis/

New Chronic Pancreatitis Clinical Trial Testing Proglumide Proglumide is now being tested in a clinical trial with the potential to target both pain and fibrosis in chronic pancreatitis.

4. withpower.com withpower.com/trial/phase-2-pancreatitis-8-2022-b8e41

Proglumide for Chronic Pancreatitis (ProCP Trial) Proglumide has been tested in rats for pancreatitis, showing some biochemical changes but not improving survival rates, and higher doses even reduced survival.

5. ddw.digitellinc.com ddw.digitellinc.com/p/s/role-of-a-cck-receptor-antagonist-proglumide-in-management-of-chronic-pancreatitis-phase-1-study-7189

ROLE OF A CCK RECEPTOR ANTAGONIST PROGLUMIDE ... Proglumide therapy may have a beneficial effect by decreasing the pain associated with CP. The change in the microRNA blood biomarkers suggests that proglumide ...