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

NCT02882477 | Unknown Phase 2

• 1 other identifier: 0003-16-HMO
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus; Iron Metabolism Disorders; Gastroduodenal Ulcer; Optic Atrophy; Sensorineural Hearing Loss; Platelet Dysfunction

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (2)

Deferiprone and Acetylcystein

EXPERIMENTAL

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

Drug: Deferiprone; Drug: Acetylcysteine

Deferiprone and Acetylcystein with Sitagliptin and Metformin

EXPERIMENTAL

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

Drug: Deferiprone; Drug: Acetylcysteine; Drug: Sitagliptin and Metformin

Interventions

Deferiprone DRUG

Also known as: Ferriprox

Deferiprone and Acetylcystein; Deferiprone and Acetylcystein with Sitagliptin and Metformin

Acetylcysteine DRUG

Also known as: Reolin

Deferiprone and Acetylcystein; Deferiprone and Acetylcystein with Sitagliptin and Metformin

Sitagliptin and Metformin DRUG

Also known as: Januet

Deferiprone and Acetylcystein with Sitagliptin and Metformin

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients who are non-cooperative.
• Patients with bone marrow disease or neutropenia.

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Hadassah medical center

Jerusalem, Israel

Location

Related Publications (12)

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  PMID: 25422446 BACKGROUND

• Amr S, Heisey C, Zhang M, Xia XJ, Shows KH, Ajlouni K, Pandya A, Satin LS, El-Shanti H, Shiang R. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am J Hum Genet. 2007 Oct;81(4):673-83. doi: 10.1086/520961. Epub 2007 Aug 20.

  PMID: 17846994 BACKGROUND

• Shang L, Hua H, Foo K, Martinez H, Watanabe K, Zimmer M, Kahler DJ, Freeby M, Chung W, LeDuc C, Goland R, Leibel RL, Egli D. beta-cell dysfunction due to increased ER stress in a stem cell model of Wolfram syndrome. Diabetes. 2014 Mar;63(3):923-33. doi: 10.2337/db13-0717. Epub 2013 Nov 13.

  PMID: 24227685 BACKGROUND

• Yamane S, Hamamoto Y, Harashima S, Harada N, Hamasaki A, Toyoda K, Fujita K, Joo E, Seino Y, Inagaki N. GLP-1 receptor agonist attenuates endoplasmic reticulum stress-mediated beta-cell damage in Akita mice. J Diabetes Investig. 2011 Apr 7;2(2):104-10. doi: 10.1111/j.2040-1124.2010.00075.x.

  PMID: 24843469 BACKGROUND

• Tamir S, Paddock ML, Darash-Yahana-Baram M, Holt SH, Sohn YS, Agranat L, Michaeli D, Stofleth JT, Lipper CH, Morcos F, Cabantchik IZ, Onuchic JN, Jennings PA, Mittler R, Nechushtai R. Structure-function analysis of NEET proteins uncovers their role as key regulators of iron and ROS homeostasis in health and disease. Biochim Biophys Acta. 2015 Jun;1853(6):1294-315. doi: 10.1016/j.bbamcr.2014.10.014. Epub 2014 Oct 23.

  PMID: 25448035 BACKGROUND

• Sohn YS, Tamir S, Song L, Michaeli D, Matouk I, Conlan AR, Harir Y, Holt SH, Shulaev V, Paddock ML, Hochberg A, Cabanchick IZ, Onuchic JN, Jennings PA, Nechushtai R, Mittler R. NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth. Proc Natl Acad Sci U S A. 2013 Sep 3;110(36):14676-81. doi: 10.1073/pnas.1313198110. Epub 2013 Aug 19.

  PMID: 23959881 BACKGROUND

• Chen YF, Kao CH, Chen YT, Wang CH, Wu CY, Tsai CY, Liu FC, Yang CW, Wei YH, Hsu MT, Tsai SF, Tsai TF. Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes Dev. 2009 May 15;23(10):1183-94. doi: 10.1101/gad.1779509.

  PMID: 19451219 BACKGROUND

• Chen YF, Wu CY, Kirby R, Kao CH, Tsai TF. A role for the CISD2 gene in lifespan control and human disease. Ann N Y Acad Sci. 2010 Jul;1201:58-64. doi: 10.1111/j.1749-6632.2010.05619.x.

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  PMID: 17084712 BACKGROUND

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  PMID: 19720788 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus; Iron Metabolism Disorders; Peptic Ulcer; Optic Atrophy; Hearing Loss, Sensorineural

Interventions

Deferiprone; Acetylcysteine; Sitagliptin Phosphate; Metformin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Duodenal Diseases; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Stomach Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Eye Diseases; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Triazoles; Azoles; Pyrazines; Biguanides; Guanidines; Amidines

Study Officials

• David Zangen, Professor

  Head of pediatric endocrinology department

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Zangen, Professor

CONTACT

0097507874488; zangend@hadassah.org.il

Ulla Najwa Abdulhag, MD

CONTACT

0097505172866; najwa.ped@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 17, 2016
• First Posted: August 29, 2016
• Study Start: December 1, 2016
• Primary Completion: May 1, 2018
• Study Completion: December 1, 2018
• Last Updated: August 29, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)