Role of a CCK Receptor Antagonist Proglumide in Management of Chronic Pancreatitis

NCT05551858 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 5063
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic pancreatitis is a rare but debilitating condition associated with chronic abdominal pain, diarrhea, diabetes, and an 8-fold increased risk for the development of pancreatic cancer. Unfortunately, there is no available treatment to prevent the progression of chronic pancreatitis, and most subjects require narcotic medications to control the pain. A receptor protein call the CCK-B receptor becomes activated in chronic pancreatitis and is in part responsible for the scar tissue or fibrosis that occurs and responsible for the cancer risk. In mice with chronic pancreatitis, the inflammation and damage was reversed with an old drug called proglumide that blocks the activation of the CCK-B receptor. Proglumide has also been shown to possibly reduce pain. This protocol involved a 2-Part study to test the safety of oral proglumide in those with confirmed chronic pancreatitis and the second goal is to determine if proglumide improves pain and function of the pancreas. Part-1 is an open-labelled Lead-in Study of N=8 subjects over a 12-week treatment period. Part-2 is a randomized double blind pseudo cross over study where subjects will be treated in Arm A (placebo for 12 weeks followed by 12 weeks of proglumide) and Arm B ( proglumide for 24 weeks).

Conditions

Safety Issues; Pain; Pancreas Fibrosis

Keywords

Cholecystokinin; Pain; Proglumide; Diabetes; Pancreatitis

Outcome Measures

Primary Outcomes (2)

• Change in blood chemistry tests

  Number of participants with abnormal chemistry blood tests at 12-weeks in placebo arm compared to treatment arm

  12 weeks of therapy

• Adverse events

  Number of Adverse events according to the Common Toxicity criteria Version 5.0 occurring in proglumide-treated compared to placebo-treated groups

  12 weeks of therapy

Secondary Outcomes (2)

• Change in Pain Measurements from baseline to end of treatment with proglumide compared to Placebo

  Baseline mean scores on a scale of 1 to 5 will be compared to scores at 12 weeks and 24 weeks

• Change in Pain Measurements numeric score from baseline to end of treatment with proglumide compared to Placebo

  Baseline mean scores compared to scores at 12 weeks and 24 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Proglumide

EXPERIMENTAL

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.

Drug: Proglumide

Interventions

Proglumide DRUG

(CAS: 6620-60-6.)

Also known as: Milid

Proglumide

Placebo DRUG

Avicel fiber filled capsule taken by mouth three times daily

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females age 18 to 75 years of age
• Clinical symptoms of chronic pancreatitis
• Plus confirmation of chronic pancreatitis with imaging (Cambridge classification), EUS, biopsy, or fecal elastase \<200µg/g, or abnormal 72 hr fecal fat and radiographic evidence of CP.
• Pain not adequately controlled with medications
• Pain of at least 5 on a numeric pain scale of 0-10
• Stable doses of anti-diabetic medication for at least 90 days prior to screening.
• Women of childbearing potential unless surgically sterile or using adequate contraception (either IUD, oral or deport contraceptive, or barrier plus spermicide).
• Both males and females must be willing and able to continue contraception to prevent pregnancy for 3 months after the completion of the study.

You may not qualify if:

• Currently abusing alcohol (more than three drinks in a day or more than seven drinks per week) or nonprescription drugs
• Pregnant or lactating, or unwilling to prevent pregnancy
• Renal insufficiency; CKD; GFR\<60
• Unable to sign consent or maintain a diary
• Liver enzymes \> 2x ULN, Hgb \<8.5, Creat\>2; HgbA1c\>8
• Type 1 Diabetes
• Subjects with confirmed cirrhosis
• Evidence of active gallbladder disease or gallbladder dyskinesia

Sponsors & Collaborators

• Georgetown University: lead

Study Sites (1)

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Related Publications (1)

• Nadella S, Ciofoaia V, Cao H, Kallakury B, Tucker RD, Smith JP. Cholecystokinin Receptor Antagonist Therapy Decreases Inflammation and Fibrosis in Chronic Pancreatitis. Dig Dis Sci. 2020 May;65(5):1376-1384. doi: 10.1007/s10620-019-05863-5. Epub 2019 Oct 9.

  PMID: 31598921 RESULT

MeSH Terms

Conditions

Pain; Diabetes Mellitus; Pancreatitis

Interventions

Proglumide

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pancreatic Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Glutamine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino

Study Officials

• Jill P Smith, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Part-2 First 12- weeks includes 1:1 drug versus placebo
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Part-1 Single group Part-2 crossover

Study Record Dates

• First Submitted: September 1, 2022
• First Posted: September 23, 2022
• Study Start: November 17, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 1, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After study complete and published
• Access Criteria: Internet

Locations

US (1)