A Phase 1/2 Trial to Test the Safety of a CCK Receptor Antagonist, Proglumide, in Management of Chronic Pancreatitis Symptoms and Pain for 12 to 24 Months
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Change in blood chemistry tests
研究概览
简要总结
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).
详细描述
Part-1 open labeled:
At screening, laboratory tests will be performed including: Liver profile, Basic chemistry with renal profile, CBC & platelets, serum lipase levels, HgbA1C, and CRP. A history and physical exam, and the numeric Pain scale diary will be provided. Subjects will be asked to record their worse pain score on a scale of 0 to 10 for each 24 hours over a seven day period. An average pain score of 5 is required for eligibility. Those meeting enrolment criteria according to lab and clinical criteria will go into the next phase.
Observation phase: Within 14 days ± 3 days, subjects that meet the inclusion criteria will have baseline Pain surveys done (Patient-Reported Outcomes Measurement Information Systems- PROMIS and COMPAT-SF) and keep a diary using the numeric pain scale (NPS) daily to record their maximum pain score for each day. The observation period will be 4 weeks. After completing the observation phase, subjects will come to CRU for the baseline visit. The pain surveys can be given to the subjects at the screening visit or sent to the subjects and completed at their home or with the assistance of the Study Coordinator on the Phone.
Baseline: At the baseline visit in the CRU, Pain diaries will be collected from the observation phase and repeat Pain Surveys will be performed (see outcomes below) and Basic chemistry with renal profile, CBC & platelets, serum lipase levels, HgbA1C, and CRP will be drawn. A history and physical exam will be performed and one red-top blood tube collected and serum frozen for a biomarker and cytokine panels. A 32-day supply of proglumide (#96) will be dispensed with instructions to administer 400mg po TID. A diary for recording pain, medication diary, recording proglumide consumption and any adverse effects will be dispensed and a follow-up appointment scheduled in 4 weeks ± 4 days.
Follow-up visits: (4 week intervals ± 3 days) Subjects will return at weeks 4, 8, 12 and 16 and bring their daily NPS diaries and medication records and bottles for review and accountability. Pain Surveys will be completed at the visits with the assistance of the study coordinator. Concomitant medications and adverse events will be reviewed. Repeat laboratory tests (same as screening) will be repeated. At weeks 4 and 8 another month's supply of proglumide will be dispensed and new diaries. At week-12 a repeat research blood tube will be collected for the biomarker investigation and for proglumide blood level analysis if needed. At weeks 12 and 16 no medication will be dispensed. The week-16 is the follow-up safety visit off medication. At each follow-up visit, subjects should also be evaluated for signs and symptoms of gallbladder pathology.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Part-2 First 12- weeks includes 1:1 drug versus placebo
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects are eligible with a history of chronic pancreatitis as defined by the Cambridge radiographic classification with abnormal pancreatic side branches but without main pancreatic duct obstructing calcifications.
- •Inclusion Criteria:
- •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.
排除标准
- •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
研究组 & 干预措施
Placebo
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.
干预措施: Placebo (Drug)
Proglumide
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.
干预措施: Proglumide (Drug)
结局指标
主要结局
Change in blood chemistry tests
时间窗: 12 weeks of therapy
Number of participants with abnormal chemistry blood tests at 12-weeks in placebo arm compared to treatment arm
Adverse events
时间窗: 12 weeks of therapy
Number of Adverse events according to the Common Toxicity criteria Version 5.0 occurring in proglumide-treated compared to placebo-treated groups
次要结局
- 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)