Efficacy and Tolerance of Liraglutide for Weight Loss in Obese Type 2 Diabetic Hemodialysis Patients (LIRADIAL)
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| ClinicalTrials.gov Identifier: NCT04529278 |
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Recruitment Status :
Recruiting
First Posted : August 27, 2020
Last Update Posted : March 31, 2022
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Diabetes Mellitus, Type 2 Hemodialysis Obese | Drug: Liraglutide | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 30 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Efficacy and Tolerance of Liraglutide for Weight Loss in Obese Type 2 Diabetic Hemodialysis Patients |
| Actual Study Start Date : | January 18, 2021 |
| Estimated Primary Completion Date : | July 17, 2023 |
| Estimated Study Completion Date : | July 17, 2023 |
| Arm | Intervention/treatment |
|---|---|
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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. |
- 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.
- 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.
- 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.
- 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.
- Glycemic balance [ Time Frame: Week 26 ]This ouctome correspond to compare the average variations in glycated hemoglobin (HbA1c) between M0 and M6.
- Hypoglycemia [ Time Frame: Week 26 ]This ouctome correspond to evaluate the percentage of hypoglycaemia between Week 1 and 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.
- Therapeutic monitoring [ Time Frame: Week 26 ]This ouctome corresponds to evaluateconcentration of liraglutide before and after the dialysis session.
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| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04529278
| Contact: Maxime Touzot, MD | 0181696111 ext +33 | maxime.touzot@auraparis.org | |
| Contact: Helene BEAUSSIER, PharmD, pHD | 0144127883 ext +33 | crc@ghpsj.fr |
| France | |
| AURA Paris Plaisance | Recruiting |
| Paris, Groupe Hospitalier Paris Saint-Joseph, France, 75014 | |
| Contact: Maxime Touzot, MD maxime.touzot@auraparis.org | |
| Principal Investigator: Maxime TOUZOT, MD | |
| Groupe Hospitalier Paris Saint-Joseph | Recruiting |
| Paris, France, 75014 | |
| Contact: Olivier Dupuy, MD odupuy@ghpsj.fr | |
| Principal Investigator: Olivier Dupuy, MD | |
| Hôpital Bichat | Recruiting |
| Paris, France, 75018 | |
| Contact: Ronan ROUSSEL, MD ronan.roussel@aphp.fr | |
| Principal Investigator: Ronan ROUSSEL, MD | |
| AURA Paris Site de Saint Ouen | Recruiting |
| Saint-Ouen, France, 93400 | |
| Contact: Pablo URENA, MD pablo.urena@auraparis.org | |
| Principal Investigator: Pablo URENA, MD | |
| Study Director: | Maxime Touzot, MD | AURA Paris Plaisance |
| Responsible Party: | Groupe Hospitalier Paris Saint Joseph |
| ClinicalTrials.gov Identifier: | NCT04529278 |
| Other Study ID Numbers: |
LIRADIAL |
| First Posted: | August 27, 2020 Key Record Dates |
| Last Update Posted: | March 31, 2022 |
| Last Verified: | March 2022 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Diabetes Mellitus, Type 2 Weight Loss Body Weight Body Weight Changes Diabetes Mellitus Glucose Metabolism Disorders Metabolic Diseases |
Endocrine System Diseases Liraglutide Hypoglycemic Agents Physiological Effects of Drugs Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |