Safety Study of High Doses of Zinc in ALS Patients
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1 Open Label Study of Zinc Therapy in ALS Patients|
- To evaluate the safety of high doses of zinc in patients with ALS [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Measure levels of BMAA in blood and urine to determine if there is a decline in these levels over the course of treatment [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||October 2010|
|Study Completion Date:||March 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
|Experimental: Zinc and Copper||
Drug: Zinc and Copper
Optizinc 90 mg/d Copper 1 mg
Physicians at Phoenix Neurological Associates (PNA) are looking for individuals diagnosed with ALS to participate in an open label phase II safety trial with zinc in conjunction with copper, used in combination with Riluzole for treating ALS. This investigator initiated trial conducted by Drs. Todd Levine and David Saperstein will help determine if zinc given at high doses is safe and tolerated and could possibly slow the progression of ALS.
Over fifty years ago an epidemic of ALS was discovered on the Island of Guam where a disease complex of ALS was found to be one hundred times more prevalent than in the rest of the world. Research on ALS in Guam linked ALS, along with Parkinson's Disease and Dementia, with a neurotoxin, β-methylamino-L-alanine (BMAA). BMAA is a non-essential amino acid and is produced by a cyanobacterium found in large concentrations in the food consumed by the people on Guam. Subsequently several groups have identified high concentrations of BMAA in brain tissues of patients from North America and Europe with several neurodegenerative diseases including ALS, Parkinson's Disease and Alzheimer's Diseases.
A small proportion of ALS, (about 2%), is associated with a mutation in the superoxide dismutase (SOD1) gene. Mice who express this mutant gene exhibit a progressive, ALS-like neurodegenerative disease.Since it is known that SOD1 binds zinc, and many of the mutant forms of this enzyme associated with ALS show altered zinc binding, zinc may play a key role in all pathological processes associated with ALS. Previous studies have shown that in ALS mutant G93A SOD transgenic mice, actual zinc supplementation delayed death. Zinc has also been thought to serve as an endogenous antioxidant in the central nervous system and help protect the BBB against oxidative stress and prevent BMAA from crossing into the brain.
It has been demonstrated that BMAA binds exceptionally strongly to transition metal ions such as zinc, copper, and nitrogen. If BMAA crossed over the permeable BBB, and enters a compartment in which glutamate was bound to zinc, then the glutamate/zinc complex would dissociate in favor of zinc having a stronger affinity to BMAA. This could lead to higher levels of unbound glutamate which is believed to be highly neurotoxic in ALS patients. We hypothesize by exposing patients to high levels of zinc, both BMAA and glutamate would be kept in a bound complex with zinc, i.e. eliminating competitive binding for zinc, which lead to less excitotoxic free glutamate and glutamate toxicity would be reduced.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01259050
|United States, Arizona|
|Phoenix Neurological Associates|
|Phoenix, Arizona, United States, 85018|
|Principal Investigator:||Todd D Levine, MD||Phoenix Neurological Associates, LTD|
|Principal Investigator:||David S Saperstein, MD||Phoenix Neurological Associates, LTD|