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
  Purpose

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 Intervention Phase
Amyotrophic Lateral Sclerosis
Drug: Zinc and Copper
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Phoenix Neurological Associates, LTD:

Primary Outcome Measures:
  • To evaluate the safety of high doses of zinc in patients with ALS [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 10
Study Start Date: October 2010
Study Completion Date: March 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zinc and Copper Drug: Zinc and Copper
Optizinc 90 mg/d Copper 1 mg

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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01259050

Locations
United States, Arizona
Phoenix Neurological Associates
Phoenix, Arizona, United States, 85018
Sponsors and Collaborators
Phoenix Neurological Associates, LTD
Investigators
Principal Investigator: Todd D Levine, MD Phoenix Neurological Associates, LTD
Principal Investigator: David S Saperstein, MD Phoenix Neurological Associates, LTD
  More Information

No publications provided

Responsible Party: Phoenix Neurological Associates, LTD
ClinicalTrials.gov Identifier: NCT01259050     History of Changes
Other Study ID Numbers: Zinc-ALS
Study First Received: December 10, 2010
Last Updated: March 9, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Phoenix Neurological Associates, LTD:
ALS treatment
Zinc
Copper
BMAA
ALS

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Pathologic Processes
Copper
Zinc
Trace Elements
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014