Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
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|ClinicalTrials.gov Identifier: NCT02882477|
Recruitment Status : Unknown
Verified August 2016 by David Zangen, Hadassah Medical Organization.
Recruitment status was: Not yet recruiting
First Posted : August 29, 2016
Last Update Posted : August 29, 2016
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus Iron Metabolism Disorders Gastroduodenal Ulcer Optic Atrophy Sensorineural Hearing Loss Platelet Dysfunction||Drug: Deferiprone Drug: Acetylcysteine Drug: Sitagliptin and Metformin||Phase 2 Phase 3|
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) .
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone, and Incretin Based Therapy|
|Study Start Date :||December 2016|
|Estimated Primary Completion Date :||May 2018|
|Estimated Study Completion Date :||December 2018|
Experimental: Deferiprone and Acetylcystein
PO Deferiprone 20 mg/kg divided in 2 doses PO Acetylcysteine 200 mg divided in 2 doses 5 months duration
Other Name: Ferriprox
Other Name: Reolin
Experimental: Deferiprone and Acetylcystein with Sitagliptin and Metformin
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
Other Name: Ferriprox
Other Name: Reolin
Drug: Sitagliptin and Metformin
Other Name: Januet
- 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 ]
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): NCT02882477
|Contact: David Zangen, Professorfirstname.lastname@example.org|
|Contact: Ulla Najwa Abdulhag, MDemail@example.com|
|Principal Investigator:||David Zangen, Professor||Head of pediatric endocrinology department|