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

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


Lead Sponsor: Hadassah Medical Organization

Source Hadassah Medical Organization
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 Description

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) Gastroscopy and gastric biopsy if the patient suffers from abdominal pain, hematemesis, melena or iron deficiency anemia or if peptic ulcer disease is clinically suspected.

Based on the routine use of the iron chelator, FDA approved, Deferiprone for Thalassemia (with detailed official guidelines of the Israel association for Pediatric Hematology) and for a similar subcellular iron accumulating disease - e.g. Friedreich Ataxia, we will initially use a dose of 20 mg per kilogram body weight (BW) daily divided in two equal doses. N-Acetylcystein an over the counter drug which also is an anti-oxidant will be given orally in the dose of 200mg twice daily to have a synergistic effect with Deferiprone.

In addition if they suffer from diabetes they will receive Januet (Sitagliptin/metformin) .

Overall Status Unknown status
Start Date December 2016
Completion Date December 2018
Primary Completion Date May 2018
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Insulin levels in blood in response to Glucose Challenge - Oral Glucose tolerance test (OGTT ) and Intra venous glucose tolerance test (IVGTT) 5 months
Platelet aggregation to Adenosine diphosphate (ADP) and Collagen - blood test for Platelet function test 5 months
Nerve conduction velocity in VEP 5 months
HBA1C level 5 months
daily glucose level measurement in the blood using Glucometer two to 5 times daily 5 months
C-Peptide levels in blood in response to Glucose Challenge - Oral Glucose tolerance test ( OGTT ) and Intra venous glucose tolerance test IVGTT 5 months
Enrollment 20

Intervention Type: Drug

Intervention Name: Deferiprone

Other Name: Ferriprox

Intervention Type: Drug

Intervention Name: Acetylcysteine

Other Name: Reolin

Intervention Type: Drug

Intervention Name: Sitagliptin and Metformin

Arm Group Label: Deferiprone and Acetylcystein with Sitagliptin and Metformin

Other Name: Januet



Inclusion Criteria:

- Male or female patients, of any age genetically and clinically diagnosed with Wolfram syndrome type 2.

Exclusion Criteria:

- Patients who are non-cooperative.

- Patients with bone marrow disease or neutropenia.

Gender: All

Minimum Age: 3 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
David Zangen, Professor Principal Investigator Head of pediatric endocrinology department
Overall Contact

Last Name: David Zangen, Professor

Phone: 0097507874488

Email: [email protected]

Facility: Contact: Contact Backup: Hadassah medical center David Zangen, Professor 0097507874488 [email protected]
Location Countries


Verification Date

August 2016

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Hadassah Medical Organization

Investigator Full Name: David Zangen

Investigator Title: Professor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Deferiprone and Acetylcystein

Type: Experimental

Description: PO Deferiprone 20 mg/kg divided in 2 doses PO Acetylcysteine 200 mg divided in 2 doses 5 months duration

Label: Deferiprone and Acetylcystein with Sitagliptin and Metformin

Type: Experimental

Description: PO Deferiprone 20 mg/kg divided in 2 doses PO Acetylcysteine 200mg divided in 2 doses PO Januet 50/500 if BW < 30kg and 50/850 if BW> 30kg *2/D 5 months duration

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)