IFPanc: Intermittent Fasting for Pancreatitis
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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N/A |
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
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Intermittent Fasting 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
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.
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Active Comparator: Control 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
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
|
Outcome Measures
Primary Outcome Measures
- Pancreas related Quality of Life Index (PANQALI) [24 weeks]
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)
Secondary Outcome Measures
- Pain scores [24 weeks]
standard score from 0-10 (0 no pain, 10 worst pain)
- Oral Morphine Equivalent Daily Dosing [24 weeks]
total dose of opiates taken converted into morphine in milligrams
- Patient weight [24 weeks]
pounds
- Patient Body mass index [24 weeks]
pounds/inch squared
- Vitamin D 25-OH levels [24 weeks]
levels of vitamin D 25-OH in nanograms/milliLiter
- stool pancreatic elastase levels [24 weeks]
stool elastase level in micrograms/gram
- Readmissions [24 weeks]
number of participants that need to seek medical care
- Length of Stay [24 weeks]
days requiring medical care
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18 year
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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
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Anatomy of chronic pancreatitis defined by Rosemont criterion9 or on imaging (CT, MRI)
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Pancreatic exocrine insufficiency defined by a pancreatic elastase < 200 ug/g stool10
Exclusion Criteria:
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Age < 18 years
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Pregnant Patients
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Age > 80 years
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Patients who cannot consent for themselves
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Glycogen storage disease
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Insulinoma or hypoglycemic state
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Active alcohol abuse
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Alcohol induced acute pancreatitis
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Gallstone induced acute pancreatitis
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Pancreatic solid neoplasm
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Patients with diabetes
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Patients on beta blockers
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
Sponsors and Collaborators
- H. Lee Moffitt Cancer Center and Research Institute
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Bellizzi AM, Bloomston M, Zhou XP, Iwenofu OH, Frankel WL. The mTOR pathway is frequently activated in pancreatic ductal adenocarcinoma and chronic pancreatitis. Appl Immunohistochem Mol Morphol. 2010 Oct;18(5):442-7. doi: 10.1097/PAI.0b013e3181de115b.
- Conwell DL, Lee LS, Yadav D, Longnecker DS, Miller FH, Mortele KJ, Levy MJ, Kwon R, Lieb JG, Stevens T, Toskes PP, Gardner TB, Gelrud A, Wu BU, Forsmark CE, Vege SS. American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines. Pancreas. 2014 Nov;43(8):1143-62. doi: 10.1097/MPA.0000000000000237.
- Corley BT, Carroll RW, Hall RM, Weatherall M, Parry-Strong A, Krebs JD. Intermittent fasting in Type 2 diabetes mellitus and the risk of hypoglycaemia: a randomized controlled trial. Diabet Med. 2018 May;35(5):588-594. doi: 10.1111/dme.13595. Epub 2018 Feb 27.
- Cotton PB, Eisen GM, Aabakken L, Baron TH, Hutter MM, Jacobson BC, Mergener K, Nemcek A Jr, Petersen BT, Petrini JL, Pike IM, Rabeneck L, Romagnuolo J, Vargo JJ. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc. 2010 Mar;71(3):446-54. doi: 10.1016/j.gie.2009.10.027.
- Crozier SJ, Sans MD, Guo L, D'Alecy LG, Williams JA. Activation of the mTOR signalling pathway is required for pancreatic growth in protease-inhibitor-fed mice. J Physiol. 2006 Jun 15;573(Pt 3):775-86. Epub 2006 Apr 13.
- Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain--United States, 2016. JAMA. 2016 Apr 19;315(15):1624-45. doi: 10.1001/jama.2016.1464. Review.
- Ferguson ND, Fan E, Camporota L, Antonelli M, Anzueto A, Beale R, Brochard L, Brower R, Esteban A, Gattinoni L, Rhodes A, Slutsky AS, Vincent JL, Rubenfeld GD, Thompson BT, Ranieri VM. The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med. 2012 Oct;38(10):1573-82. Epub 2012 Aug 25. Erratum in: Intensive Care Med. 2012 Oct;38(10):1731-2.
- Han S, Patel B, Min M, Bocelli L, Kheder J, Wachholtz A, Wassef W. Quality of life comparison between smokers and non-smokers with chronic pancreatitis. Pancreatology. 2018 Apr;18(3):269-274. doi: 10.1016/j.pan.2018.02.012. Epub 2018 Feb 26.
- Herzig KH, Purhonen AK, Räsänen KM, Idziak J, Juvonen P, Phillps R, Walkowiak J. Fecal pancreatic elastase-1 levels in older individuals without known gastrointestinal diseases or diabetes mellitus. BMC Geriatr. 2011 Jan 25;11:4. doi: 10.1186/1471-2318-11-4.
- Javle MM, Shroff RT, Xiong H, Varadhachary GA, Fogelman D, Reddy SA, Davis D, Zhang Y, Wolff RA, Abbruzzese JL. Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: results of two phase II studies. BMC Cancer. 2010 Jul 14;10:368. doi: 10.1186/1471-2407-10-368.
- Ji L, Li L, Qu F, Zhang G, Wang Y, Bai X, Pan S, Xue D, Wang G, Sun B. Hydrogen sulphide exacerbates acute pancreatitis by over-activating autophagy via AMPK/mTOR pathway. J Cell Mol Med. 2016 Dec;20(12):2349-2361. doi: 10.1111/jcmm.12928. Epub 2016 Jul 15.
- Law R, Leal C, Dayyeh BA, Leise MD, Balderramo D, Baron TH, Cardenas A. Role of immunosuppression in post-endoscopic retrograde cholangiopancreatography pancreatitis after liver transplantation: a retrospective analysis. Liver Transpl. 2013 Dec;19(12):1354-60. doi: 10.1002/lt.23758.
- Wassef W, DeWitt J, McGreevy K, Wilcox M, Whitcomb D, Yadav D, Amann S, Mishra G, Alkaade S, Romagnuolo J, Stevens T, Vargo J, Gardner T, Singh V, Park W, Hartigan C, Barton B, Bova C. Pancreatitis Quality of Life Instrument: A Psychometric Evaluation. Am J Gastroenterol. 2016 Aug;111(8):1177-86. doi: 10.1038/ajg.2016.225. Epub 2016 Jun 14.
- Wu XM, Ji KQ, Wang HY, Zhao Y, Jia J, Gao XP, Zang B. MicroRNA-339-3p alleviates inflammation and edema and suppresses pulmonary microvascular endothelial cell apoptosis in mice with severe acute pancreatitis-associated acute lung injury by regulating Anxa3 via the Akt/mTOR signaling pathway. J Cell Biochem. 2018 Aug;119(8):6704-6714. doi: 10.1002/jcb.26859. Epub 2018 Apr 25. Retraction in: J Cell Biochem. 2021 Nov;122 Suppl 1:S107.
- Yang J, Waldron RT, Su HY, Moro A, Chang HH, Eibl G, Ferreri K, Kandeel FR, Lugea A, Li L, Pandol SJ. Insulin promotes proliferation and fibrosing responses in activated pancreatic stellate cells. Am J Physiol Gastrointest Liver Physiol. 2016 Oct 1;311(4):G675-G687. doi: 10.1152/ajpgi.00251.2016. Epub 2016 Sep 8.
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