Fracture Risk After Pancreas Transplantation (FraPaT) (FRAPAT)

Effect of Type 1 Diabetes Remission by Pancreas Transplantation Alone on Fracture Risk: a Retrospective Matched Cohort Study

Individuals with type 1 diabetes (T1D) are at greater risk of fracture than non-diabetic subjects. Although the mechanisms underlying bone fragility in T1D are not completely understood, insulin deficiency seems to play a key role.

To date, no information is available on the effect of diabetes remission after pancreatic transplantation alone (PTA) on the risk of fractures in T1D individuals with preserved kidney function.

The overall objective of this retrospective cohort study is to evaluate the effect of T1D remission after PTA on fracture risk.

The primary endpoint will be the difference in fracture incidence (any fracture) between the PTA group and the control group. For the PTA group, the incidence of fractures after transplantation will be considered.

Data from patients who underwent PTA at IRCCS San Raffaele Hospital from January 2, 2005 to December 31, 2017 will be compared with age-, gender- and disease duration-matched controls from the pool of outpatients with T1D attending the Endocrinology Unit at the same Institution. Anthropometric, anamnestic, laboratory data and data on the history of fractures and past/current therapies will be collected.

With this study, for the first time we will be able to obtain information on the effects of diabetes remission on the risk of fracture. We expect that the remission of diabetes will result in a beneficial effect on the fracture risk.

Study Overview

• Status: Completed
• Conditions: Fractures, Bone; Diabetes Mellitus, Type 1
• Intervention / Treatment: Procedure: Pancreas transplantation alone

• Study Type: Observational
• Enrollment (Actual): 81

Contacts and Locations

Study Locations

• Italy
  • Please Select
    • Milan, Please Select, Italy, 20123
      • San Raffaele Scientific Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients who underwent their first deceased donor PTA, or second deceased donor PTA if their first graft was explanted within a week, at the IRCCS San Raffaele Hospital between 2 January 2005 and 31 December 2017 will be screened for this study. Controls will be selected among outpatients with T1D attending the Endocrinology Unit at IRCCS San Raffaele Hospital and those listed for a first deceased donor PTA.

Description

Inclusion Criteria (PTA group)

• T1D patients who received their first PTA, or second PTA only if their first graft was explanted within a week, between 2 January 2005 and 31 December 2017
• age ≥18 and < 65 years
• willingness to participate in this observational study

Inclusion Criteria (control group)

• Type 1 diabetes
• age ≥18 years and < 65 years
• willingness to participate in this observational study
• minimum disease duration of 5 years
• brittle diabetes, as defined by the occurrence of frequent acute complications (ketoacidosis or severe hypoglycaemic episodes requiring third-part assistance or unawareness despite well-conducted intensive insulin therapy)
• presence of at least one diabetes-related complication (either neuropathy, retinopathy, subclinical nephropathy).

Exclusion Criteria (both groups)

• conditions other than T1D known to affect bone health (i.e., non-compensated hypothyroidism, hyperthyroidism, hyperparathyroidism, inflammatory bowel disease, malignancy, rheumatoid arthritis, hypogonadism, severe chronic obstructive pulmonary disease, hepatic insufficiency, alcohol intake ≥ 3 units/day ),
• use of drugs that can affect bone metabolism (e.g., bisphosphonates, anticonvulsants, hormone replacement therapy) other than glucocorticoids and immunosuppressants
• recipients of simultaneous pancreas kidney transplantation, pancreatic islet transplantation, multiple PTAs, other transplants
• BMI <18.5 or ≥ 30 kg/m2

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PTA; patients who underwent their first deceased donor PTA, or second deceased donor PTA if their first graft was explanted within a week, at the IRCCS San Raffaele Hospital between 2 January 2005 and 31 December 2017	Procedure: Pancreas transplantation alone; Pancreas transplantation
Controls; outpatients with T1D attending the Endocrinology Unit at IRCCS San Raffaele Hospital and patients listed for a first deceased donor PTA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fracture incidence	Difference in fracture incidence (any fracture) between the PTA and the control group	02 January 2005 - 30 September 2018

Collaborators and Investigators

• Sponsor: Università Vita-Salute San Raffaele

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2019
• Primary Completion (Actual): March 2, 2020
• Study Completion (Actual): December 24, 2020

Study Registration Dates

• First Submitted: March 8, 2019
• First Submitted That Met QC Criteria: March 8, 2019
• First Posted (Actual): March 11, 2019

Study Record Updates

• Last Update Posted (Actual): December 29, 2020
• Last Update Submitted That Met QC Criteria: December 27, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Wounds and Injuries; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Fractures, Bone; Gastrointestinal Agents; Pancrelipase
• Other Study ID Numbers: FRAPAT; 155/INT/2018 (Other Identifier: Ethics Committee)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No