Safety Study of High Doses of Zinc in ALS Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Phoenix Neurological Associates, LTD
ClinicalTrials.gov Identifier:
NCT01259050
First received: December 10, 2010
Last updated: March 9, 2012
Last verified: March 2012

December 10, 2010
March 9, 2012
October 2010
January 2012   (final data collection date for primary outcome measure)
To evaluate the safety of high doses of zinc in patients with ALS [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01259050 on ClinicalTrials.gov Archive Site
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 ]
Same as current
Not Provided
Not Provided
 
Safety Study of High Doses of Zinc in ALS Patients
Phase 1 Open Label Study of Zinc Therapy in ALS Patients

The purpose of this study is to determine the safety of Zinc given at 90mg/d in conjunction with 2mg/d of copper in ALS patients.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Amyotrophic Lateral Sclerosis
Drug: Zinc and Copper
Optizinc 90 mg/d Copper 1 mg
Experimental: Zinc and Copper
Intervention: Drug: Zinc and Copper
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
March 2012
January 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Age 18-85
  2. Male or Female
  3. Clinically definite or probable ALS by El Escorial criteria
  4. ALS-FRS > 25
  5. If on Riluzole they must be on a stable dose for at least 30 days prior to screening
  6. Capable of providing informed consent and complying with trial procedures

Exclusion Criteria:

  1. Patients with FVC below 50%
  2. History of liver disease
  3. Severe renal failure
  4. Creatinine greater than or equal to 1.5 mg/dL
  5. History of intolerance to zinc or copper
  6. Evidence of motor neuron disease for greater than 5 years
  7. Any other co-morbid condition which would make completion of the trial unlikely
  8. If female, pregnant or breast-feeding; or, if of childbearing age, an unwillingness to use birth control.
  9. Any other trial medications. Non-trial medications are not cause for exclusion
  10. Patient with history of significant anemia
  11. Elevated levels of zinc at baseline
  12. Patients with copper levels below normal at baseline
Both
18 Years to 85 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01259050
Zinc-ALS
Yes
Phoenix Neurological Associates, LTD
Phoenix Neurological Associates, LTD
Not Provided
Principal Investigator: Todd D Levine, MD Phoenix Neurological Associates, LTD
Principal Investigator: David S Saperstein, MD Phoenix Neurological Associates, LTD
Phoenix Neurological Associates, LTD
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP