Prevention of Microvascular Complications in Overweight Diabetics With Surgery or Best Medicine (PROMISE)

Prevention of Microvascular Complications in Overweight Diabetics With Surgery or Best Medicine; a Prospectivee, Randomized, Multicenter Study

Background: Diabetic kidney disease (DKD) is chronic and often progresses to kidney failure,heart disease and premature death. Unfortunately, the best medical therapies available for DKD today are ultimately unable to prevent its progression, especially in obese patients.Surgical rerouting of food within the gut with a gastric bypass operation (RYGB), improves diabetes and some of its complications.

The investigators propose to investigate whether RYGB in combination with best medical therapy in patients with DKD and obesity prevent further deterioration of kidney function over a 3 years follow up period.

Study design: This is an international collaboration with leading centres in Sweden and Switzerland in which100 obese type 2 diabetic patients with established DKD will volunteer to be randomly assigned to receive best medical therapy with RYGB or best medical therapy without surgery. Participants will be 18-65 years with type 2 diabetes and impaired kidney function. Yearly measurements of kidney function will then be done over a period of 3 years as a primary outcome to determine whether differences in DKD can be detectable. The study will also examine and compare a) safety of the interventions, b) the health economic impact on direct healthcare costs and Quality of Life in patients as well as c) the value of a new marker of DKD in determining which patients are most likely to benefit from surgery.

Overall the study will strengthen the evidence base guiding clinical decisions about the usefulness of RYGB as an add on therapy to best medical therapy in stopping progressive DKD in patients with obesity and diabetes.

Study Overview

• Status: Withdrawn
• Conditions: Diabetic Kidney Disease
• Intervention / Treatment: Procedure: Optimal medical treatment and surgery; Procedure: Optimal medical treatment

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 116 28
    • Ersta Hospital
• Switzerland
  • Basel, Switzerland, 4058
    • St:Claraspital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • BMI 28 - 35 kg/m2

  • Age: 18-65 years, with T2DM
  • Estimated glomerular filtration rate (eGFR; by MDRD) between 30 and 60mL/min/1.73m2
  • Urine albumin creatinine ratio (ACR) of at least 30mg/g (microalbuminuria) in first void urine on two separate days.

Exclusion Criteria:

• • Type 1 diabetes or a positive GAD antibody test

  • Known renal artery stenosis
  • Renal impairment for reasons unrelated to diabetes
  • Suspicion of glomerulonephritis as determined by urine sediment (>10 erythrocytes/visual field)
  • Post-renal obstruction diagnosed by ultrasound
  • Severe retinopathy (defined as high-risk proliferative diabetic retinopathy and severe visual loss according to the "Early Treatment Diabetic Retinopathy Study Severity Scale")
  • Severe DKD (CKD 4 or 5, requirement of renal replacement therapy such as dialysis or kidney transplantation)
  • Severe neuropathy (peripheral neuropathy stage 3)
  • Unacceptably high risk for general anesthesia
  • Prior extensive intra-abdominal surgery making laparoscopy complicated
  • Myocardial infarction, cerebrovascular accident, transient ischemic attack, coronary-artery bypass grafting or percutaneous transluminal coronary angioplasty within the previous 6 months
  • Cardiac failure (NYHA stage > 2)
  • Inability to stop smoking prior to inclusion
  • Pregnancy or breast feeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Optimal medical treatment and surgery; In the study 50 obese patients with CKD 3 andT2DM will be treated using the European Association for Study of Diabetes protocol in combination with RYGB surgery.	Procedure: Optimal medical treatment and surgery
Other: Optimal medical treatment; In the study 50 obese patients with CKD 3 andT2DM will be treated using the European Association for Study of Diabetes protocol	Procedure: Optimal medical treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glomerular filtration rate	Renal function measurement by Iohexol clearance	Three years after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microvascular kidney damage	Microvascular kidney damage measured by Albumin/Creatinine Ratio	3 years after intervention
Glycaemic control	HbA1c and fasting plasma glucose measurements . Five day continuous glucose monitoring	3 years after intervention
peripheral nervous system function	Michigan Neuropathy Screening Instrument (MNSI) score, which includes two separate assessments: a lower extremity examination that includes inspection of the feet to identify deformities, dry skin, calluses, infection, fissure, or ulcers, and assessment of vibratory sensation and ankle reflexes	3 years after intervention
autonomic nervous system function	Autonomic neuropathy will be assessed with the RR intervals on ECG during deep breathing test	3 years after intervention
diabetic eyes complications	Using retinal photos and using the International Clinical Diabetic Retinopathy Disease Severity Scale	3 years after intervention
blood preassure	Blood pressure will be recorded with calibrated and validated electronic blood pressure equipment and appropriate sized cuff. Patients will sit in a chair in a quiet room for 5 minutes.	3 years after intervention
Lipids	Total cholesterol, low density lipoprotein, high density lipoprotein cholesterol and triglycerides will be measured	3 years after intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
health economics	Direct healthcare resource consumption. Costs to Governments or Insurance companies plus private expenditure on health. Costs will include primary and secondary surgery, medication, laboratory tests, health provider reimbursement, private prescription charges and co-payments for medications	from intervention and three years forward
Quality of life score	Quality of life will be measured by the general health 36-item Health Survey (SF-36)	three years after intervention

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Collaborators: St. Claraspital AG
• Investigators: Principal Investigator: Thorell Anders, Professor, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Anticipated): January 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: December 10, 2013
• First Submitted That Met QC Criteria: December 12, 2013
• First Posted (Estimate): December 13, 2013

Study Record Updates

• Last Update Posted (Actual): March 13, 2017
• Last Update Submitted That Met QC Criteria: March 10, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Body Weight; Kidney Diseases; Diabetic Nephropathies; Overweight
• Other Study ID Numbers: 2013/1530-31