Clinical trial NCT01099332: Trial of Novel Oral Zinc Cysteine Preparation in Alzheimer's Disease
Official title: CopperProof-2: Prospective, Randomized, Double-Blind Placebo-Controlled Clinical Trial Comparing the Effects of a Novel Once-Daily Oral Zinc Cysteine Preparation on Zinc and Copper Parameters in Mild Cognitive Impairment and Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Alzheimer's Disease
Mild Cognitive Impairment
Keywords: Alzheimer's disease
Mild Cognitive Impairment
Copper metabolism
Zinc metabolism
Ceruloplasmin
Lead sponsor: Adeona Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2010-04-07
Enrollment: 60
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial aims to test the hypothesis that 1) a single dose of zinc cysteine in a proprietary gastro-retentive form will produce sustained blood levels of zinc giving a larger bioavailable amount of zinc than an FDA approved preparation of inorganic zinc acetate; and 2) that the zinc cysteine gastro-retentive, sustained-release preparation will be better tolerated with significantly less gastrointestinal side effects than the zinc acetate capsules. The trial also tests the hypothesis that, after 6 months of once daily administration, the zinc cysteine subjects will show reduced serum non-ceruloplasmin copper. Additionally, subjects will perform tests of mental function,including the dementia rating scale, the Mini Mental Status Examination and the ADAS-cognitive performance test aimed at Alzheimer's status assessment. Tests will be administered at baseline, 3 and 6 months, and the performance results compared. Care-giver assessments will also be noted.

Detailed description: This multi-center study aims to determine the pharmacokinetics and pharmacodynamics of a novel gastro-retentive, sustained-release zinc cysteine preparation on the blood and urine measures of copper and zinc balance in Alzheimer's disease and mild cognitive impairment. Data expected to be derived include tolerability of the novel preparation in comparison with oral inorganic zinc salt, and long-term effects on primarily blood-measured copper-zinc balance. The study design is that of a prospective, randomized, double blind placebo-controlled clinical trial, with a duration for individual subjects of 6 months. The study will be performed at a total of 3 sites, under the direction of a single principal investigator, with a sub-investigator. The statistical plan calls for a comparison of data from the two long-term parallel groups using ANOVA and other applicable techniques. In addition to blood parameters, mental function assessments obtained at baseline, 3 and 6 months will be evaluated statistically.

Eligibility criteria: Inclusion Criteria:

* Alzheimer's disease mild to moderate as diagnosed by standard clinical, functional and NINDA-ADRDA criteria
* Mild cognitive impairment diagnosed by standard clinical, functional and NINDA-ADRDA criteria
* All subjects able to swallow Tablets
* Subjects taking copper or zinc containing supplements must have a 30-day wash out before starting study materials
* Screening laboratory values either within normal limits or deemed not clinically significant by investigator

Exclusion Criteria:

* Subjects or their study companions/care givers unable to give adequate informed consent
* Presence of a disease or condition known to affect biometal homeostasis
* Presence of psychosis, substance abuse or other major medical or neurological issues
* Presence of vascular dementia
* Clinically significant anemia at the time of the screening visit
* Current use of a decoppering drug such as trientine or penicillamine

Primary outcomes:
measure: Biometal levels will be measured in serum by atomic absorption spectrometry
timeFrame: 6 to 12 months
Secondary outcomes:
measure: Serum zinc levels after oral administration of two different zinc-containing compounds and placebo will be determined by atomic absorption spectrometry
timeFrame: 3 months
measure: Comparison of mental status functions at baseline, 3 and 6 months in active comparator versus placebo groups.
timeFrame: 6 to 12 months
Other outcomes:
Locations:
city: Clearwater
country: United States
facility: Neuroscience Research Unit
state: Florida
city: Holiday
country: United States
facility: ATIT Neurology
state: Florida
city: Port Richey
country: United States
facility: The Cottages
state: Florida
Study officials:
affiliation: Senior Vice President of Research and Development, Adeona Pharmaceuticals, Inc.
name: David Newsome, M.D.
role: STUDY_DIRECTOR
References:
citation: Squitti R, Bressi F, Pasqualetti P, Bonomini C, Ghidoni R, Binetti G, Cassetta E, Moffa F, Ventriglia M, Vernieri F, Rossini PM. Longitudinal prognostic value of serum "free" copper in patients with Alzheimer disease. Neurology. 2009 Jan 6;72(1):50-5. doi: 10.1212/01.wnl.0000338568.28960.3f.
citation: Arnal N, Cristalli DO, de Alaniz MJ, Marra CA. Clinical utility of copper, ceruloplasmin, and metallothionein plasma determinations in human neurodegenerative patients and their first-degree relatives. Brain Res. 2010 Mar 10;1319:118-30. doi: 10.1016/j.brainres.2009.11.085. Epub 2009 Dec 22.
citation: Brewer GJ, Newsome DA et al. Sub-clinical zinc deficiency found in Alzheimer's disease. Presented at ICAD, Vienna,Austria; July 2009 09-HT-2656-ALZ; submitted for publication