Clinical Trial: Observational Study of Deferiprone (Ferriprox®) in the Treatment of Superficial Siderosis

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Observational

Official Title: Phase IV Observational Study of Deferiprone (Ferriprox®) in the Treatment of Superficial Siderosis

Brief Summary:

Superficial siderosis is a progressive neurological disease caused by iron deposition in the central nervous system from chronic subarachnoid bleeding. Until 2011, there has been no effective treatment for this progressive condition that leads to hearing loss, spasticity, weakness, loss of bowel/bladder function, incoordination, dementia and ultimately death.

Last year, we demonstrated that a lipid soluble iron chelator, deferiprone, can reduce hemosiderin deposition in patients with superficial siderosis by MRI in as little as 3 months. As the only therapy that can improve this condition, chelation with deferiprone is the standard of care for treatment of superficial siderosis. Now that the FDA has approved deferiprone in the United States for thalassemia, we propose documenting the clinical effect of deferiprone over 2 years in superficial siderosis patients. Our goal is to understand how the clinical course of this disease is altered using standard of care chelation therapy with deferiprone.

Patients with superficial siderosis who are taking deferiprone for chelation therapy at doses consistent with the standard of care will be offered enrollment into this observational study. Patients will be treated and monitored locally by participating neurologists who have agreed to help us collect information for this study. We are interested in documenting the clinical effect of deferiprone on hearing, ataxia and myelopathy using standardized scales performed and documenting the effect of deferiprone on hemosiderin deposition in the CNS by MRI, all performed according to standard of care.


Detailed Summary:

First described over 100 years ago, superficial siderosis is a rare neurodegenerative disease caused by iron toxicity in the CNS due to chronic subarachnoid bleeding. Iron from red blood cells in the subarachnoid space is preferentially taken up by the Bergmann glia in the cerebellum, brainstem, spinal cord, eighth cranial nerve and the cerebral cortex; the iron is stored as ferritin within the glial cells. With continued subarachnoid bleeding, the glia are overwhelmed by the ferritin load and die. Their loss exposes neurons to free iron which is toxic to cells because it catalyzes the breakdown of hydrogen peroxide to superoxide, a reactive oxygen species that can cause lipid peroxidation, membrane dysfunction, and neuronal cell death.

Neurological consequences of iron overload depend on the area of the brain exposed to free iron. With chronic subarachnoid bleeding, the blood tends to pool around the brainstem, cerebellum and spinal cord thus leading to the classic triad of hearing loss, ataxia and myelopathy that is seen in more than 50% of patients with superficial siderosis. The eighth cranial nerve courses through the subarachnoid space until it reaches the inner ear exposing it to the toxic blood; in contrast, the other cranial nerves are protected by the peripheral Schwann cells within 1 mm of exiting the brainstem. Compared to the other CNS structures affected in superficial siderosis, the eighth cranial nerve is the most susceptible because it exposes the most surface area to volume. Thus, the most common and often the first symptom patients get is sensorineural hearing loss. This is followed by ataxia due to dysfunction of both the vestibular component of the eighth cranial nerve and neurodegeneration of the cerebellum. Myelopathy develops when the brainstem and spinal cord are involved. With continued bleeding, other areas of the brain can degenerate leading to
Sponsor: Johns Hopkins University

Current Primary Outcome:

  • Efficacy -- Improvement in hearing audiology exam [ Time Frame: 2 years ]
    Standard audiology exam to examine severity and frequency and hearing loss in both ears.
  • Ashworth Spasticity Scale score as a measure of muscle spasticity [ Time Frame: 2 years ]
    Standardized score to measure changes in limb muscle spasticity
  • Scale for the Assessment and Rating of Ataxia [ Time Frame: 2 years ]
    Standardized outcome measure to measure changes in coordination function including ability to stand, walk, talk and move the arms and legs in a coordinated manner.


Original Primary Outcome: Safety -- Number of patients who report an adverse event [ Time Frame: 90 days ]

Monitoring for white blood cell counts, liver function tests, ferritin and reticulocyte hemoglobin equivalent, as well as monitoring for adverse events such as constipation, diarrhea, joint pains and muscle aches.


Current Secondary Outcome: MRI of the brain and spinal cord [ Time Frame: every 6 months for 2 years ]

MRI of the brain and spinal cord without contrast to monitor for changes in hemosiderin deposition.


Original Secondary Outcome:

  • Ashworth Spasticity Scale score as a measure of muscle spasticity [ Time Frame: 90 days ]
    Standardized score to measure changes in limb muscle spasticity
  • Scale for the Assessment and Rating of Ataxia [ Time Frame: 90 days after starting drug ]
    Standardized outcome measure to measure changes in coordination function including ability to stand, walk, talk and move the arms and legs in a coordinated manner.


Information By: Johns Hopkins University

Dates:
Date Received: January 20, 2011
Date Started: March 2012
Date Completion: June 2017
Last Updated: December 20, 2016
Last Verified: December 2016