Efficacy and Tolerance of Liraglutide for Weight Loss in Obese Type 2 Diabetic Hemodialysis Patients (LIRADIAL)

April 13, 2023 updated by: Groupe Hospitalier Paris Saint Joseph

Diabetes is the second leading cause of end stage renal disease in France (22% in the 2016 REIN register). In hemodialysis, its prevalence is higher, between 30-40% depending on the study. Associated with type 2 diabetes, a large number of patients present with overweight (body mass index or BMI> 25 kg / m2) which can lead to a temporary contraindication to kidney transplant by the surgeon, or even definitive once BMI is over 30 kg / m2. Indeed, above this threshold, patients are exposed to an increased risk of surgical complications (wall infections, suture release), hospitalizations and potentially transplant failure. A recent study based on the Kidney Registry showed that patients with a BMI> 31 kg / m2 were more likely to stay on dialysis than to benefit from a transplant whereas for each decrease of 1 kg / m2 of BMI, there is a 9-11% increase in the likelihood of being transplanted. The management of obesity in dialysis patients is important for reducing cardiovascular risks but also because it increases the chances of access to transplantation. However, current weight loss programs are disappointing. The changes in hygiene and diet rules integrated into a specialized monitoring program only allow a weight loss of 2 to 8% in 24 months for half of the patients. Bariatric surgery is, of course, a more effective alternative, but with a 10% risk of postoperative complications.

Glucagon-Like Peptide 1 (aGLP1) analogues are a new class of antidiabetic drugs that have revolutionized the management of type 2 diabetes. In fact, they combine efficacy on glycemic control but also on weight loss. They are used in obese non-diabetic people in some countries, with a reduction in weight of up to 10 to 15% with certain molecules. In addition, they have shown an effect on reducing cardiovascular events in diabetics including with Chronic Kidney Disease CKD 3-4. AGPL1 are well tolerated with side effects mainly of digestive tropism such as nausea or vomiting. Exceptionally, these effects can occur from the first injection requiring permanent discontinuation of treatment. In 20% of cases, these side effects can appear in the first weeks. They gradually fade, spontaneously or after symptomatic treatment and allow titration of the drug.

AGLP1 is currently contraindicated in patients with reduced renal function, that is, when the glomerular filtration rate (GFR) is <15 ml / min (MRC stage 5-5D), because this population specific was excluded from the originator studies. However, aGLP1 are small peptides that are not eliminated by the kidneys. Their elimination takes place through the general catabolism of proteins. To date, 2 publications have evaluated the safety profile and efficacy of an aGLP1, liraglutide (Victoza®), in diabetic dialysis patients. These studies showed that the 24 hour plasma concentration of liraglutide increased by 50% over the long term. The safety profile was acceptable with, as expected, a predominance of gastrointestinal effects in the first weeks of treatment such as nausea, vomiting. The authors suggest an adjustment of the dosages and a longer titration period to limit side effects. However, treatment with aGPL1 is effective with better glycemic control and an average weight loss of 2.6 kg over a period of 3 months. Studies show that weight loss under liraglutide continues beyond 3 months with possible losses between 4 and 8 kg at 6 months and 12 months of treatment followed 12. Liraglutide (Victoza®) is the analogue of GPL1 for which we have a sufficiently long follow-up (> 10 years) on its effectiveness and its short and long-term side effects.

The main objective of this project, in type 2 diabetic patients on dialysis, as a temporary contraindication for transplant due to overweight, is on the one hand to study the effect of liraglutide on weight loss and control of diabetes, and on the other hand to assess its tolerance in this population. The expected benefit is to be able to facilitate registration on the waiting list and access to renal transplantation of these overweight patients, without having to resort to more invasive methods such as bariatric surgery.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Paris, France, 75014
        • Groupe Hospitalier Paris Saint-Joseph
      • Paris, France, 75018
        • Hôpital Bichat
      • Saint-Ouen, France, 93400
        • AURA Paris Site de Saint Ouen
    • Groupe Hospitalier Paris Saint-Joseph
      • Paris, Groupe Hospitalier Paris Saint-Joseph, France, 75014
        • AURA Paris Plaisance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patient aged ≥ 18 and <70
  • Patient on hemodialysis for more than 6 months
  • Type 2 diabetic patient
  • Patient with a BMI> 30 kg / m2 with a Temporary Contraindication for kidney transplant for renal transplant due to overweight by his graft center
  • Patient affiliated to a health insurance plan
  • French speaking patient
  • Patient having given free, informed and written consent

Exclusion Criteria:

  • Patient with a Temporary Contraindication for kidney transplant for a cause other than overweight
  • Patient with personal or family history of thyroid medullary cancer
  • Patient with a history of acute or chronic pancreatitis
  • Patient who has already had hypersensitivity to liraglutide (or to any other component of the product)
  • Patient who has already had a severe digestive intolerance to taking GLP-1 receptor agonists (such as exenatide or lixisenatide)
  • Patient already included in an interventional risk research protocol (RIPH1)
  • Pregnant or lactating woman
  • Patient under guardianship or curatorship
  • Patient deprived of liberty

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Liraglutide

Liraglutide is initiated at 0.6 mg / day during week S1 (initiation D1) during weekly hospitalization in the diabetology department. Then the dose of liraglutide is increased to 1.2 mg / day on week S2 (increase in dose on D8) then to 1.8 mg / day on week S3 (increase in dose on D15).

The daily dose is then 1.8 mg until week W26.
Drug: Liraglutide

Liraglutide is initiated at 0.6 mg / day during week S1 (initiation D1) during weekly hospitalization in the diabetology department. Then the dose of liraglutide is increased to 1.2 mg / day on week S2 (increase in dose on D8) then to 1.8 mg / day on week S3 (increase in dose on D15).

The daily dose is then 1.8 mg until week W26.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Weight Loss at Week 26
Time Frame: Week 26
This outcome corresponds to Assess weight loss in obese diabetic patients on hemodialysis after 6 months of treatment with liraglutide in order to facilitate access to renal transplants for patients who have been rejected for being overweight.
Week 26

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lift of CIT for transplant for obesity
Time Frame: Week 26
This outcome corresponds to establish the number and percentage of patients whose CIT transplant for obesity will be lifted after 6 months of treatment.
Week 26
Tolerance of luraglutide
Time Frame: Week 26
This outcome corresponds to evaluate the number and percentage of serious and non-serious adverse events in type 2 diabetic patients on hemodialysis.
Week 26
Regulation of blood sugar
Time Frame: Week 26
This ouctome correspond to evaluate the reducing the number / dose of anti-diabetic drugs or the daily dose of insulin.
Week 26
Glycemic balance
Time Frame: Week 26
This ouctome correspond to compare the average variations in glycated hemoglobin (HbA1c) between M0 and M6.
Week 26
Hypoglycemia
Time Frame: Week 26
This ouctome correspond to evaluate the percentage of hypoglycaemia between Week 1 and Week 26.
Week 26
Evolution of weight
Time Frame: Week 26
This ouctome corresponds to evaluate the modifications of the dry mass and the fatty mass between M0 and M6 by bioimpedancemetry.
Week 26
Therapeutic monitoring
Time Frame: Week 26
This ouctome corresponds to evaluateconcentration of liraglutide before and after the dialysis session.
Week 26

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Groupe Hospitalier Paris Saint Joseph

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 18, 2021

Primary Completion (Actual)

January 17, 2023

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

August 21, 2020

First Submitted That Met QC Criteria

August 25, 2020

First Posted (Actual)

August 27, 2020

Study Record Updates

Last Update Posted (Actual)

April 14, 2023

Last Update Submitted That Met QC Criteria

April 13, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LIRADIAL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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