Intermittent Fasting for Pancreatitis

Pancreatitis Clinical Trial

— IFPanc  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04760847
• Other study ID #: STUDY20201373
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 7, 2024
• Est. completion date: April 1, 2026

Study information

• Verified date: June 2024
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: Shaffer Mok
• Phone: 6099804564
• Email: mok.shaffer[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 64
• Est. completion date: April 1, 2026
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Recurrent Pancreatitis
• Pancreas Disease
• Pancreatic Diseases
• Pancreatitis
• Pancreatitis, Acute
• Pancreatitis, Chronic

Intervention

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.
• 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

Locations

Country	Name	City	State
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (15)

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. — View Citation

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. — View Citation

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. — View Citation

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. No abstract available. — View Citation

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. doi: 10.1113/jphysiol.2006.106914. Epub 2006 Apr 13. — View Citation

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. — View Citation

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. doi: 10.1007/s00134-012-2682-1. Epub 2012 Aug 25. Erratum In: Intensive Care Med. 2012 Oct;38(10):1731-2. — View Citation

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. — View Citation

Herzig KH, Purhonen AK, Rasanen 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

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