Trial of Novel Oral Zinc Cysteine Preparation in Alzheimer's Disease

Mild Cognitive Impairment Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01099332
• Other study ID #: CopperProof-2
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: March 30, 2010
• Last updated: January 27, 2011
• Start date: November 2009
• Est. completion date: January 2011

Study information

• Verified date: January 2011
• Source: Adeona Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 55 Years to 90 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Cognition Disorders
• Mild Cognitive Impairment

Intervention

Other:
• Gastro-retentive zinc cysteine tablet
Oral, one tablet, once daily with water for 6 months.
• Tablet identical physically to active comparator containing some lactose
Oral, once daily, with water, 6 months.

Locations

Country	Name	City	State
United States	Neuroscience Research Unit	Clearwater	Florida
United States	ATIT Neurology	Holiday	Florida
United States	The Cottages	Port Richey	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Adeona Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biometal levels will be measured in serum by atomic absorption spectrometry	Active comparator material orally administered will be associated with better tolerability than oral zinc acetate, and will produce a reduction in serum non-ceruloplasmin bound copper levels and an elevation in serum zinc levels	6 to 12 months	No
Secondary	Serum zinc levels after oral administration of two different zinc-containing compounds and placebo will be determined by atomic absorption spectrometry	The change in serum zinc levels over time after oral administration of the active comparator of the study as well as the placebo and for certain subjects an inorganic zinc salt will be compared	3 months	No
Secondary	Comparison of mental status functions at baseline, 3 and 6 months in active comparator versus placebo groups.	All subjects will perform standard and standardized tests of mental function, ranging from a general dementia rating scale (Mini Mental Status Exam) to more Alzheimer's specific tests (ADAS-cognitive). Daily living and caregiver assessments of overall daily functioning will be noted. Test results will be compared statistically in a two-point fashion, and correlated with biometal ststus.	6 to 12 months	No