Safety Study of High Doses of Zinc in ALS Patients

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

Phase 1 Open Label Study of Zinc Therapy in ALS Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01259050
• Other study ID #: Zinc-ALS
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: December 10, 2010
• Last updated: March 9, 2012
• Start date: October 2010
• Est. completion date: March 2012

Study information

• Verified date: March 2012
• Source: Phoenix Neurological Associates, LTD
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: March 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease

Intervention

Drug:
• Zinc and Copper
Optizinc 90 mg/d Copper 1 mg

Locations

Country	Name	City	State
United States	Phoenix Neurological Associates	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Phoenix Neurological Associates, LTD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the safety of high doses of zinc in patients with ALS		1 year
Secondary	Measure levels of BMAA in blood and urine to determine if there is a decline in these levels over the course of treatment		1 year