Amyotrophic Lateral SclerosisPhase 1/2NCT01259050
Safety Study of High Doses of Zinc in ALS Patients
A Phase 1/2 study testing Zinc and Copper in people with Amyotrophic Lateral Sclerosis, run by Phoenix Neurological Associates, LTD at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Zinc and Copper
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to Mar 2012
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-85
- Male or Female
- Clinically definite or probable ALS by El Escorial criteria
- ALS-FRS > 25
- If on Riluzole they must be on a stable dose for at least 30 days prior to screening
- Capable of providing informed consent and complying with trial procedures
Who cannot join
- Patients with FVC below 50%
- History of liver disease
- Severe renal failure
- Creatinine greater than or equal to 1.5 mg/dL
- History of intolerance to zinc or copper
- Evidence of motor neuron disease for greater than 5 years
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- Any other co-morbid condition which would make completion of the trial unlikely
- If female, pregnant or breast-feeding; or, if of childbearing age, an unwillingness to use birth control.
- Any other trial medications. Non-trial medications are not cause for exclusion
- Patient with history of significant anemia
- Elevated levels of zinc at baseline
- Patients with copper levels below normal at baseline
Trial locations and contacts
1 site in 1 country.
United States1 site
Phoenix Neurological Associates
Phoenix, Arizona, 85018
About this study
Official title: 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.
Read the 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.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Zinc and Copper
- Keywords
- ALS treatment, Zinc, Copper, BMAA, ALS
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zinc and CopperDrug
Optizinc 90 mg/d Copper 1 mg
| Study group | Role | What they receive |
|---|---|---|
| Zinc and Copper | Experimental | Not described Receives: Drug: Zinc and Copper |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety of high doses of zinc in patients with ALS
Measured: 1 year
Secondary outcomes (1)
Measure levels of BMAA in blood and urine to determine if there is a decline in these levels over the course of treatment
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2010 (estimated)
- Study startOct 2010
- Primary completionJan 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Phoenix Neurological Associates, LTD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Todd D Levine, MD, Principal investigator, Phoenix Neurological Associates, LTDDavid S Saperstein, MD, Principal investigator, Phoenix Neurological Associates, LTD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01259050
- Sponsor's protocol ID
- Zinc-ALS
- Status last verified
- Mar 2012
- First submitted
- 10 Dec 2010
- Last updated
- 12 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Open Label Study of Zinc Therapy in ALS Patients
- ClinicalTrials.gov ID
- NCT01259050
- Acronym / sponsor ID
- Zinc-ALS
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS treatment, Zinc, Copper, BMAA, ALS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Phoenix Neurological Associates, LTDUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Jan 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 13 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Zinc and Copper | Experimental | Drug: Zinc and Copper |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18-85
- Male or Female
- Clinically definite or probable ALS by El Escorial criteria
- ALS-FRS > 25
- If on Riluzole they must be on a stable dose for at least 30 days prior to screening
Key exclusion criteria (12 listed)
- Patients with FVC below 50%
- History of liver disease
- Severe renal failure
- Creatinine greater than or equal to 1.5 mg/dL
- History of intolerance to zinc or copper
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zinc and CopperOptizinc 90 mg/d Copper 1 mg | Drug | Zinc and Copper |
Primary outcome
To evaluate the safety of high doses of zinc in patients with ALS
Time frame: 1 year
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Todd D Levine, MD principal investigator
Phoenix Neurological Associates, LTD
David S Saperstein, MD principal investigator
Phoenix Neurological Associates, LTD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Zinc and Copper in people with Amyotrophic Lateral Sclerosis, run by Phoenix Neurological Associates, LTD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the safety of high doses of zinc in patients with ALS (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2012.