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Safety Study of High Doses of Zinc in ALS Patients

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ClinicalTrials.gov Identifier: NCT01259050
Recruitment Status : Completed
First Posted : December 13, 2010
Last Update Posted : March 12, 2012
Information provided by (Responsible Party):
Phoenix Neurological Associates, LTD

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: Zinc and Copper Phase 1 Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Open Label Study of Zinc Therapy in ALS Patients
Study Start Date : October 2010
Actual Primary Completion Date : January 2012
Actual Study Completion Date : March 2012

Arm Intervention/treatment
Experimental: Zinc and Copper Drug: Zinc and Copper
Optizinc 90 mg/d Copper 1 mg

Primary Outcome Measures :
  1. To evaluate the safety of high doses of zinc in patients with ALS [ Time Frame: 1 year ]

Secondary Outcome Measures :
  1. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

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): NCT01259050

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United States, Arizona
Phoenix Neurological Associates
Phoenix, Arizona, United States, 85018
Sponsors and Collaborators
Phoenix Neurological Associates, LTD
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Principal Investigator: Todd D Levine, MD Phoenix Neurological Associates, LTD
Principal Investigator: David S Saperstein, MD Phoenix Neurological Associates, LTD
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Responsible Party: Phoenix Neurological Associates, LTD
ClinicalTrials.gov Identifier: NCT01259050    
Other Study ID Numbers: Zinc-ALS
First Posted: December 13, 2010    Key Record Dates
Last Update Posted: March 12, 2012
Last Verified: March 2012
Keywords provided by Phoenix Neurological Associates, LTD:
ALS treatment
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Trace Elements
Physiological Effects of Drugs