Intermittent Fasting for Pancreatitis

Study Overview
=================
Brief Summary
-----------------
The purpose of this research is to compare intermittent fasting with a standard diet approach for improving the quality of life related to your pancreas disease. Our hope is to improve your symptoms and prevent you from needing to go into the hospital for pancreas-related issues.

Detailed Description
-----------------
Fasting is a classic means for religious discipline, yet recently regaining favor in the medical landscape. Numerous studies have come forth, both in animals and humans outlining the benefit of intermittent fasting (IF) on various disease states and longevity. Though a relatively complex cellular process, fasting for at least 8-12 hours has been shown to lead to fatty acid release from a patient's adipose storage. These fatty acids then shuttle to the liver, where they are converted to ketones such as beta-hydroxybutyrate and acetoacetate. Ketones are then utilized for energy sources in the heart, brain and skeletal muscle tissue. The energy produced (ATP), then leads to increase in the cellular powerhouses, the mitochondria and autophagy or cell recycling. This cellular recycling is one main way in which IF has proven benefit for inflammatory conditions and in cancer care. Furthermore, reductions in amino acids and glucose due to fasting and reliance on ketones as energy, lead to down regulation of the membrane target of rapamycin (mTOR) pathway. Much is known regarding the mTOR pathway. Down regulation of mTOR is associated with increased autophagy (as above), lower protein and lipid synthesis, ribosome and lysosome creation (cell shuttles) and lowered energy use. Specific to the pancreas, mTOR down regulation has been shown to lower protein synthesis with the pancreas, caused by cholecystokinin (CCK), a pancreas stimulating hormone.2 The effect of this leads to lower pancreatic enzymes secretion. Inhibition of mTOR also lowers the generation of fibroblasts, the scar-tissue cells within the pancreas, leading to less scar-formation.3 Scar tissue formation is a vital part of morbidity and complications for patients with chronic pancreatitis. Pancreatic disease-modulation has also been evaluated in regard to the mTOR pathway.4 For pancreatic cancer, rapamycin a mTOR inhibitor have been implicated as targets for chemotherapy. Clinical trials have shown benefit for pancreatic cancer cases given rapamycin in concert with other chemotherapeutic medications.5 For acute, chronic pancreatitis and post-ndoscopic retrograde cholangiopancreatopgraphy (ERCP) pancreatitis, mTOR is usually activated.6 In particular, blocking the mTOR pathway can favor autophagy, limit cell death (apoptosis) and hence necrosis of the pancreas. Necrosis in pancreatitis, leads to complex disease, possess a higher mortality, organ failure, and can make the clinical course more complicated. Therefore, the mTOR pathway has been implicated as a potential therapeutic target to ameliorate disease course and severity.4,7,8 The purpose of this study is to evaluate IF as a means for limiting disease severity with people who have recurrent acute pancreatitis and chronic pancreatitis. Our hypothesis is that IF will improve pancreatic-disease related quality of life.1

Official Title
-----------------
Intermittent Fasting as a Primary Means for Improving Quality of Life for Acute and Chronic Pancreatitis

Conditions
-----------------
Acute Recurrent Pancreatitis, Pancreatitis, Pancreatitis, Acute, Pancreatitis, Chronic, Pancreas Disease

Intervention / Treatment
-----------------
* Other: Intermittent Fasting
* Other: No intermittent fasting


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 year Recurrent acute pancreatitis defined by greater than 2 episodes of pancreatitis, defined by: abdominal pain and either amylase or lipase > 3 x the upper limit of normal, imaging suggestive of, separated by time Anatomy of chronic pancreatitis defined by Rosemont criterion9 or on imaging (CT, MRI) Pancreatic exocrine insufficiency defined by a pancreatic elastase < 200 ug/g stool10 Exclusion Criteria: Age < 18 years Pregnant Patients Age > 80 years Patients who cannot consent for themselves Glycogen storage disease Insulinoma or hypoglycemic state Active alcohol abuse Alcohol induced acute pancreatitis Gallstone induced acute pancreatitis Pancreatic solid neoplasm Patients with diabetes Patients on beta blockers

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The control group will have 32 patients and the group undergoing IF will have 32 patients (for both recurrent acute and chronic pancreatitis); the randomization is 1:1; IF versus control. Sixty four subjects will be enrolled at UH for a total of 64 subjects.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intermittent Fasting<br>Patients in Group A will then receive information regarding intermittent fasting, which would include fasting for a 16-hour period each day, followed by ingestion of an appropriate number of calories for the remaining part of the day. | Other: Intermittent Fasting<br>* These subjects will will then receive information regarding intermittent fasting, which would include fasting for a 16-hour period each day, followed by ingestion of an appropriate number of calories for the remaining part of the day. See attached IF Quick Facts for details provided to the patient.<br>|
| Active Comparator: Control<br>These subjects will undergo standard caloric dietary guidance. Patients in group B will also be given the above information, though not be asked to intermittently fast. | Other: No intermittent fasting<br>* These subjects will undergo standard caloric dietary guidance. Patients in group B will also be given the above information, though not be asked to intermittently fast<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pancreas related Quality of Life Index (PANQALI) | Pancreas related Quality of Life Index (PANQALI) is pancreas related quality of life index scale from 0 (lowest or better disease activity) to 90 (highest or worse disease activity) | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain scores | standard score from 0-10 (0 no pain, 10 worst pain) | 24 weeks | 
| Oral Morphine Equivalent Daily Dosing | total dose of opiates taken converted into morphine in milligrams | 24 weeks | 
| Patient weight | pounds | 24 weeks | 
| Patient Body mass index | pounds/inch squared | 24 weeks | 
| Vitamin D 25-OH levels | levels of vitamin D 25-OH in nanograms/milliLiter | 24 weeks | 
| stool pancreatic elastase levels | stool elastase level in micrograms/gram | 24 weeks | 
| Readmissions | number of participants that need to seek medical care | 24 weeks | 
| Length of Stay | days requiring medical care | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pancreatitis, acute pancreatitis, acute recurrent pancreatitis, chronic pancreatitis, fasting, intermittent fasting