Role of Pancreatic Exocrine Secretion in Weight Gain After Pancreas Transplantation

Weight Gain Clinical Trial

Official title:

Role of Pancreatic Exocrine Secretion in Weight Gain After Pancreas Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04690738
• Other study ID #: 20052109
• Status: Recruiting
• Start date: August 17, 2020
• Est. completion date: December 31, 2030

Study information

• Verified date: December 2023
• Source: Rush University Medical Center
• Contact: Amanda Van Jacobs, MS
• Phone: 312.563.0490
• Email: Amanda_C_VanJacobs[@]rush.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Pancreas transplantation is currently the most reliable method for glycemic control in insulin dependent diabetic patients. Outcomes of pancreas transplantation have improved significantly over the years due to improved surgical techniques, medical management and immunosuppression. However, weight gain after pancreas transplantation remains a common problem with associated consequences such as development of type 2 diabetes, coronary artery disease, graft loss, metabolic syndrome and increased risk of cardiovascular death. Excessive weight gain is well known after liver and kidney transplantation; however there are very few studies that have looked at weight gain after pancreas transplantation. In a recent study by Knight et al, 26% of the pancreas transplant recipients had excessive weight gain, defined as more than 30% of their baseline weight by 1-year post transplant. The study focused mainly on the endocrine function of the pancreas, explaining that excessive peripheral insulin circulation post-transplant may explain the weight gain. Other factors like immunosuppression, increased oral intake and potentially reduced activity may also have played a role. However no study has looked at the possible role of exocrine secretion from the new pancreatic allograft, combined with exocrine secretion of the old pancreas, leading to excessive availability of digestive juices like trypsin, chymotrypsin, lipase, amylase, gelatinase, elastase etc. Our hypothesis is that the excessive weight gain after pancreas transplant, which is more than in other solid organ transplants, is driven by the excessive digestive juice leading to improved conversion of available food and nutrient into storable energy and subsequently leading to weight gain. The patient will therefore need to either increase physical activity to avoid weight gain post-transplant or significantly reduce caloric intake.

Fecal elastase test (FE-1)-elastase is a proteolytic enzyme produced by pancreatic acinar cells. They bind to bile salt and pass through the gut without degradation. These levels correlate well with the other pancreatic enzyme levels. Fecal elastase concentration (FEC) has been used routinely to screen for pancreatic exocrine insufficiency (PEI).

Exocrine pancreatic juice has been a target for the management of obesity lately, with the use of drugs like Orlistat (Xenical) that inhibits pancreatic lipase and therefore interfere with the absorption of fat. If our theory of excessive pancreatic juice availability after pancreas transplant can be proven, it can help guide the targeted use and appropriate dosing of such drugs based on the level of the pancreatic juice as measured by the FEC.

Description:

This is the second of a two-part study. The first part, a pilot study, assessed the FEC level after pancreas transplant to determine if FEC is high compared to that of the general population and see if particularly high levels correlate with post pancreas transplant weight gain. The pilot study demonstrated excessively high FEC relative to the general population/healthy individuals, and much higher than the upper limit of the assay. However, the study did not show correlation between weight gain and high post-transplant FEC. This is thought to be because majority of the subjects enrolled were years from their transplant and the high FEC and weight gain already occurred early post-transplant. The study showed that FEC level was particularly high early post-transplant and decreased gradually over the years. It also showed that most weight gain occurred between years

1 to 2 post-transplant; we therefore felt the pilot study might have missed the period when the high level of exocrine secretion contributed to the weight gain. The primary aim of this second part is to assess patients from pre-transplant period to post-transplant period and see if FEC early posttransplant correlates with weight gain, particularly during the period of post-transplant weight gain established from results of the pilot study. The relationship between obesity and the gut microbiome is still not well established. To understand the role of gut microbiome in pancreas transplant patients, we will assess gut microbiome and other gut factors that may help us determine if the weight gain is related to lifestyle changes or it is associated with pancreas transplant.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2030
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Recipients of pancreas transplant with or without other organs

• Age 18 - 80 yrs

Exclusion Criteria:

• Unwillingness to consent or participate in the study

Related Conditions & MeSH terms

• Body Weight
• Exocrine Pancreatic Insufficiency
• Weight Gain

Intervention

Diagnostic Test:
• Fecal Elastase Concentration
Stool sample for fecal elastase-1 (FEC) analysis and microbiome for sequencing and analysis will be obtained pre- and post-transplant.

Locations

Country	Name	City	State
United States	Rush University Medical Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Rush University Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (4)

Dominguez-Munoz JE, D Hardt P, Lerch MM, Lohr MJ. Potential for Screening for Pancreatic Exocrine Insufficiency Using the Fecal Elastase-1 Test. Dig Dis Sci. 2017 May;62(5):1119-1130. doi: 10.1007/s10620-017-4524-z. Epub 2017 Mar 17. — View Citation

Ewald N, Raspe A, Kaufmann C, Bretzel RG, Kloer HU, Hardt PD. Determinants of Exocrine Pancreatic Function as Measured by Fecal Elastase-1 Concentrations (FEC) in Patients with Diabetes mellitus. Eur J Med Res. 2009 Mar 17;14(3):118-22. doi: 10.1186/2047-783x-14-3-118. — View Citation

Forsmark C, Adams PC. Pancreatic function testing--valuable but underused. Can J Gastroenterol. 2009 Aug;23(8):529-30. doi: 10.1155/2009/464326. No abstract available. — View Citation

Knight RJ, Islam AK, Pham C, Graviss EA, Nguyen DT, Moore LW, Kagan A, Sadhu AR, Podder H, Gaber AO. Weight Gain After Simultaneous Kidney and Pancreas Transplantation. Transplantation. 2020 Mar;104(3):632-639. doi: 10.1097/TP.0000000000002862. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of Fecal Elastase-1, measured in mcg/g, correlation with post-transplant weight		Follow-up for up to 3 years post-transplant