Clinical Trial: Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone, and Incretin Based Therapy

Brief Summary: Patients who are genetically diagnosed with the recently reported and rare Wolfram syndrome type 2 ( WFS2) and have the degenerative and symptomatic disease including signs such as diabetes, platelet aggregation defect or visual problems will be asked to participate in this study. Knowing the pathomechanism of WFS2 with rapid cell death, after doing baseline investigations to asses the severity of their disease, the participants will be offered a chelator therapy with in addition to the antioxidant Acetylcystein, in diabetic patients an Incertin (GLP-1 ) therapy will be offered as well. The baseline investigations will be repeated after 2 months and after 5 months of therapy in order to asses the progression of the disease and to show if the chelator and anti oxidant therapy and in diabetic patients the GLP-1 therapy could stop the progression of the disease.

Detailed Summary:

In WFS2 mutation the protein nutrient-deprivation autophagy factor-1(NAF-1) is affected.

Given the known result of NAF-1 protein dysfunction in animal and cultured cell line models namely a toxic accumulation of iron in the mitochondria,leading to mitochondrial destruction and oxidative stress we aim to obtain fibroblast samples from the patients and (use laboratory fibroblasts from healthy subjects as controls) These cell cultures will initially be studied for intracellular iron accumulation and then re-evaluated following treatment by Deferiprone and/or Glucagon-like peptide 1 (GLP-1) ex-vivo in the laboratory .

If repeated (n>=3) histological evidence confirms the beneficial effect of Deferiprone and/or GLP-1(incertin based therapy) in the patient's cultured fibroblasts by reversing the toxic iron accumulation in the patient's mitochondria to a normal level, he/she will be offered "in vivo" therapy using the oral chelating agent - with or without dipeptidylpeptidase-4 inhibitor (DPP-4) inhibitors or GLP-1 receptor agonists. Adding GLP-1 based therapy will depend on the diabetic status of the patient.

Prior and following 60 and 150 days of Chelator and/or GLP-1 therapy they will go through the following clinical and laboratory evaluations which will establish the baseline and post therapeutic parameters (outcome) to be compared:

detailed medical history and physical examination complete blood count (CBC) and iron levels platelet aggregation studies Fundoscopy and visual evoked potentials (VEP) Hearing evaluation Oral glucose Tolerance Test optional Intra venous glucose tolerance test (IVGTT) /glucagon/arginine test HBA1C Daily profile of blood glucose Optional CGMS ( continuous glucose monitoring system) Gastr
Sponsor: Hadassah Medical Organization

Current Primary Outcome:

  • Insulin levels in blood in response to Glucose Challenge - Oral Glucose tolerance test (OGTT ) and Intra venous glucose tolerance test (IVGTT) [ Time Frame: 5 months ]
  • Platelet aggregation to Adenosine diphosphate (ADP) and Collagen - blood test for Platelet function test [ Time Frame: 5 months ]
  • Nerve conduction velocity in VEP [ Time Frame: 5 months ]
  • HBA1C level [ Time Frame: 5 months ]
  • daily glucose level measurement in the blood using Glucometer two to 5 times daily [ Time Frame: 5 months ]
  • C-Peptide levels in blood in response to Glucose Challenge - Oral Glucose tolerance test ( OGTT ) and Intra venous glucose tolerance test IVGTT [ Time Frame: 5 months ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Hadassah Medical Organization

Dates:
Date Received: July 17, 2016
Date Started: December 2016
Date Completion: December 2018
Last Updated: August 24, 2016
Last Verified: August 2016