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

Primary Purpose

Alzheimer's Disease, Mild Cognitive Impairment

Status

Unknown status

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Gastro-retentive zinc cysteine tablet

Tablet identical physically to active comparator containing some lactose

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's disease, Mild Cognitive Impairment, Copper metabolism, Zinc metabolism, Ceruloplasmin

Eligibility Criteria

55 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Neuroscience Research Unit
ATIT Neurology
The Cottages

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Gastro-retentive zinc cysteine tablet

Identical appearance of placebo with active comparator

Arm Description

Once daily administration by mouth of a gastro-retentive, sustained-release preparation of zinc cysteine with excipients, all G.R.A.S., with adequate water.

Once daily administration of placebo of identical physical appearance to that of active comparator with similar amount of water.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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.

Full Information

NCT ID

NCT01099332

First Posted

March 30, 2010

Last Updated

January 27, 2011

Sponsor

Adeona Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01099332

Brief Title

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

2. Study Status

Record Verification Date

January 2011

Overall Recruitment Status

Unknown status

Study Start Date

November 2009 (undefined)

Primary Completion Date

January 2011 (Anticipated)

Study Completion Date

January 2011 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Adeona Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer's Disease, Mild Cognitive Impairment

Keywords

Alzheimer's disease, Mild Cognitive Impairment, Copper metabolism, Zinc metabolism, Ceruloplasmin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Gastro-retentive zinc cysteine tablet

Arm Type

Active Comparator

Arm Description

Once daily administration by mouth of a gastro-retentive, sustained-release preparation of zinc cysteine with excipients, all G.R.A.S., with adequate water.

Arm Title

Identical appearance of placebo with active comparator

Arm Type

Placebo Comparator

Arm Description

Once daily administration of placebo of identical physical appearance to that of active comparator with similar amount of water.

Intervention Type

Other

Intervention Name(s)

Gastro-retentive zinc cysteine tablet

Other Intervention Name(s)

Zinthionein ZC

Intervention Description

Oral, one tablet, once daily with water for 6 months.

Intervention Type

Other

Intervention Name(s)

Tablet identical physically to active comparator containing some lactose

Other Intervention Name(s)

Placebo Tablet

Intervention Description

Oral, once daily, with water, 6 months.

Primary Outcome Measure Information:

Title

Biometal levels will be measured in serum by atomic absorption spectrometry

Description

Time Frame

6 to 12 months

Secondary Outcome Measure Information:

Title

Serum zinc levels after oral administration of two different zinc-containing compounds and placebo will be determined by atomic absorption spectrometry

Description

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

Time Frame

3 months

Title

Comparison of mental status functions at baseline, 3 and 6 months in active comparator versus placebo groups.

Description

Time Frame

6 to 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

55 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Newsome, M.D.

Organizational Affiliation

Senior Vice President of Research and Development, Adeona Pharmaceuticals, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Neuroscience Research Unit

City

Clearwater

State/Province

Florida

ZIP/Postal Code

33756

Country

United States

Facility Name

ATIT Neurology

City

Holiday

State/Province

Florida

ZIP/Postal Code

34691

Country

United States

Facility Name

The Cottages

City

Port Richey

State/Province

Florida

ZIP/Postal Code

34668

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

19122030

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.

Results Reference

background

PubMed Identifier

20026314

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.

Results Reference

background

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

Results Reference

background

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

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