Combined Bariatric Surgery and Pancreas After Kidney Transplantation for Type II Diabetics (ComB-PAK)

The goal of this clinical trial is to evaluate the effectiveness of sleeve gastrectomy combined with pancreas after kidney (PAK) transplantation as a means of achieving normoglycemia, insulin independence, reduced insulin resistance, and kidney graft function preservation in the T2DM population. in the first year post pancreas after kidney transplant. Safety and efficacy data will be collected from the time of enrollment until participants reach 1 year post PAK transplant. Data will be compared to historical data from TGH's renal and pancreas transplant programs.

Study Overview

• Status: Enrolling by invitation
• Conditions: Diabetes Mellitus, Type 2; Overweight
• Intervention / Treatment: Procedure: Sleeve Gastrectomy AND Pancreas after Kidney Transplantation (Staggered Approach); Procedure: Combined Sleeve Gastrectomy and Pancreas transplantation

Detailed Description

Diabetes is the leading cause of renal dysfunction and failure in Canada. Many patients will require dialysis and some with qualify for and receive a renal transplant. While a renal transplant can restore kidney function in diabetics, it does not address the underlying cause of the kidney disease. Patients remain at high risk of future morbidity from diabetes, including cardiovascular disease, retinopathy, neuropathy, and damage to the new graft. Notably, hyperglycemia is the largest risk factor to the renal bed. Good control of blood glucose levels is essential to minimize these effects but is not easily achieved or maintained.

Pancreas transplantation eliminates the use of exogenous insulin and normalizes glucose levels in the blood. Patients with Type I diabetes are routinely offered Pancreas transplant -either Pancreas After Kidney (PAK) or Simultaneous -pancreas-kidney (SPK). In rare circumstances, patients can also receive a pancreas alone (PTA). At UHN, the investigators have offered SPK transplants to select patients with type II DM who are within weight criteria (BMI <30), but the investigators do not routinely offer PAK transplants to patients with DMII as these patients are overweight and suffering from insulin resistance. Patients with DMII may not be able to achieve normoglycemia and may continue to require exogenous insulin supplementation, after PAK alone.

Weight loss in severely overweight individuals with DMII is known to improve insulin sensitivity. The majority of patients with DM II are overweight and have associated metabolic syndrome. Obesity and metabolic syndrome are themselves major risk factors for poor long-term outcomes in kidney transplantation. Weight loss can lead to improvements in all metabolic syndrome diagnostic criteria, however, it can be difficult to achieve significant and sustained weight loss in the context of insulin resistance associated with DM II. Patients who have already received a kidney transplant have the added metabolic side effects of immunosuppressive medications.

To ensure excellent long-term outcomes with kidney transplantation, it is critically important to investigate strategies to minimize obesity, control diabetes, and improve metabolic and cardiovascular risk factors. Weight loss can be achieved through dieting and exercise, but most patients who diet regain their former weight or gain additional weight. Sleeve gastrectomy (SG) is an aggressive but well-tolerated treatment for obesity which can lessen the risk factors associated with metabolic syndrome and associated poor transplant outcomes.

The investigators hypothesize that combining SG and PAK in patients with DM II who have previously undergone renal transplant will result in improvement of glycemic control, metabolic syndrome criteria, preserved/improved renal graft function and be well tolerated.

This study will investigate the safety and efficacy of SG prior to PAK (staggered approach) compared to simultaneous SG and PAK (combined approach). Safety and efficacy data will be compared to historical data from TGH's renal and pancreas transplant programs. Controls will consist of DMII patients having undergone kidney transplant only, and DMII patients having undergone SPK.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • Toronto General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to provide informed consent
• Females must be post-menopausal, surgically sterile or practicing adequate birth control for the duration of the study period
• Recipient of a kidney graft (either live or deceased donor) due to diabetic nephropathy
• Minimum 6 months post-Kidney transplantation surgery
• BMI >30

• Possess 3 of 4 metabolic syndrome components

  • Elevated waist circumference (>88cm for women; >102cm for men)
  • Elevated Triglycerides (>150mg/dL) or drug treatment for elevated triglycerides
  • Low HDL cholesterol (<40mg/dL for men; <50mg/dL for women)
  • Elevated blood pressure (systolic >130mmHg or diastolic >85mmHg) or hypertensive drug treatment
• T2DM - fasting c-peptide of >900 pmol/L
• insulin dependent >1 year

Exclusion Criteria:

• eGFR < 60
• Abnormal alb/cr ratio >2.9
• Cigarette, cigar or pipe smoking; Occasional cannabis smoking is allowable, but not recommended
• Significant peripheral vascular disease that would prevent pancreas from safely being implanted (this is assessed as part of SOC pancreas transplant workup)
• Previous bariatric surgery
• Presence of any other condition that could compromise the patient's ability to safely undergo, or benefit from SG procedure.
• Known BK nephropathy or significant vascular damage to the kidney graft

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Staggered Approach; The first 10 participants enrolled will undergo Sleeve Gastrectomy a minimum of 3 months prior to Pancreas Transplant.	Procedure: Sleeve Gastrectomy AND Pancreas after Kidney Transplantation (Staggered Approach); Participants will undergo sleeve gastrectomy a minimum of 3 months prior to Pancreas Transplant. SG will be performed using the standard technique. Pancreas transplant will be performed as per standard procedure.
Experimental: Group 2: Combined Approach; Eligible participants will undergo SG and pancreas transplantation simultaneously	Procedure: Combined Sleeve Gastrectomy and Pancreas transplantation; Simultaneous SG and pancreas transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients achieving normoglycemia	The primary study endpoint will be the proportion of patients who achieve normoglycemia (as defined by HbA1c <6%) by Month 12 post-PAK. This will be compared to the proportion of patients among the historical controls who achieve normoglycemia through medical treatment alone and have undergone kidney transplant alone or simultaneous pancreas-kidney transplantation.	month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body weight (kg) from baseline to post-SG (group 1); baseline to post-Pancreas Tx M3 (group 2)	Change in body weight (kg) from baseline to post-SG (group 1); baseline to post-Pancreas Tx M3 (group 2)	month 3
Change in body weight (kg) from baseline to post-PAK	Change in body weight (kg) from baseline to post-PAK	month 12
Change in HbA1c levels	Change in HbA1c levels	month 12
Body mass index (BMI)	Body mass index (BMI)	month 12
Waist circumference	Waist circumference	month 12
Change in renal graft function post-PAK	Change in renal graft function measured by creatinine/urea and Alb/Creatinine ratio	months 3,6, 9 and 12
HbA1c levels post-SG	HbA1c levels post-SG (group 1)	month 3
HbA1c levels post-PAK	HbA1c levels post-PAK	months 3,6, 9 and 12
Proportion of participants with morbid obesity post PAK	Proportion of participants with morbid obesity (defined as BMI > 35) post PAK	month 12

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Trevor Reichman, University Health Network, Toronto

Publications and helpful links

General Publications

• AlEnazi NA, Ahmad KS, Elsamahy IA, Essa MS. Feasibility and impact of laparoscopic sleeve gastrectomy after renal transplantation on comorbidities, graft function and quality of life. BMC Surg. 2021 May 4;21(1):235. doi: 10.1186/s12893-021-01138-x.
• Viscido G, Gorodner V, Signorini FJ, Campazzo M, Navarro L, Obeide LR, Moser F. Sleeve Gastrectomy after Renal Transplantation. Obes Surg. 2018 Jun;28(6):1587-1594. doi: 10.1007/s11695-017-3056-0.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2022
• Primary Completion (Anticipated): June 30, 2026
• Study Completion (Anticipated): June 30, 2026

Study Registration Dates

• First Submitted: October 7, 2022
• First Submitted That Met QC Criteria: October 7, 2022
• First Posted (Actual): October 12, 2022

Study Record Updates

• Last Update Posted (Actual): October 24, 2022
• Last Update Submitted That Met QC Criteria: October 20, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Body Weight; Diabetes Mellitus, Type 2; Overweight; Gastrointestinal Agents; Pancrelipase; Pancreatin
• Other Study ID Numbers: 21-5927

Drug and device information, study documents

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