Study of the Effects of Cerefolin NAC on Inflammation Blood Markers in Older Individuals With Memory Complaints

Study Overview
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Brief Summary
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The purpose of this six-month research study is to determine if Cerefolin NAC reduces levels of substances in the blood that may be associated with thinking ability and the health of brain cells in subjects with memory concerns when compared to a standard multivitamin. Cerefolin NAC is available as a dietary supplement via a prescription from a physician. The multivitamin used in the study contains the Recommended Daily Intake recommended for older persons.

Detailed Description
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Study Phase: Exploratory Indication: Memory Complaints Study Design: A single-center, double-blind, placebo-controlled study with 100 subjects with memory complaints followed for 6 months (4 visits)using Cerefolin® NAC or placebo once a day in addition to a standardized multivitamin. Sample Size: 100 subjects as follows: 50 on Cerefolin® NAC + multivitamin; and, 50 on Placebo + multivitamin. Primary Objective: To determine if Cerefolin® NAC (compared to multivitamin) decreases the blood level of homocysteine, increases the blood level of glutathione (a marker for oxidative stress), and increases the ratio of Aβ42 to Aβ40 (a marker for beta-amyloid) that may be related to neuronal injury and inflammation. Secondary Objectives: To determine if Cerefolin® NAC reduces hs-CRP and TNF-α blood levels, and increases IL-6 blood levels. To determine if Cerefolin® NAC (compared to Placebo) reduces plasma F2 isoprostane and increases potential antioxidant (PAO) levels. To assess the tolerability of Cerefolin® NAC To explore the effects of Cerefolin® NAC on a 6-month change in: (a)global and specific cognitive domains in a standardized neuropsychological test battery,(b) quality of life as measured by SF-36, (c)instrumental and basic activities of daily living, (d)MADRS; and (e)performance-based physical function. To explore if a change in homocysteine level is related to a change in the plasma glutathione, hs-CRP, IL-6, TNF-α, F2-isoprostane, and PAO levels and to a change in the ratio of Aβ42 to Aβ40. To explore the effects of MS AG2756, APOE and MFTHR on the relationship examined in Secondary Objective #5. To explore the relationship of B12 status and status to cognition NOTE: For individuals successfully completing the 6-month blinded phase, there is an 12-month open-label extension of Cerefolin NAC + multivitamin. The primary purpose of the exploratory, open-label extension phase of the CERE-001 study is to systematically collect long-term safety data on CEREFOLIN NAC usage over an additional 12-month period.

Official Title
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A Six-month, Double-blind, Placebo-controlled, Single Site Study of Cerefolin NAC on Blood Homocysteine, Oxidative Stress, and Beta-amyloid Biomarkers That May Potentiate Inflammation and Neuronal Damage in Older Individuals With Memory Complaints Who Have Not Been Clinically Diagnosed With Mild Cognitive Impairment, Vascular Dementia, or Alzheimer's Disease

Conditions
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Subjective Memory Loss in Older Persons

Intervention / Treatment
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* Other: Cerefolin NAC (a medical food)
* Other: Cerefolin NAC placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 60; Memory complaints as defined by two questions: Do The subject think your have memory problems?; and, Has there been a decline in your memory over the last 10 years? Fluency in English; Ability to ingest oral medications; and, Willing to replace current vitamin intake with a standardized multivitamin provided for the study. Exclusion Criteria: Clinical stroke or Parkinson's disease; Taking FDA approved drug for symptomatic treatment of Alzheimer's disease (Aricept, Razadyne, Exelon, and/or Namenda); History of significant renal insufficiency (creatinine ≥1.5); History of renal stones or peptic ulcer disease; Use of vitamin supplements containing more than 400mcg of folic acid per day within 2 months of Screen Visit; As determined by the study physician, clinically significant serum folate and vitamin B12 deficiency on screening blood tests that would require further clinical evaluation and treatment As determined by the study physician, clinically significant medical conditions, physical exam findings or abnormal blood tests at screening that would require further clinical evaluation and treatment B12 injections 6 months prior to the Screen Visit; Confirmed clinical diagnosis of Mild Cognitive Impairment (MCI), vascular dementia or Alzheimer's Disease (AD); and, Known hypersensitivity to L-methylfolate, methyl-cobalamin or N-acetylcysteine. Use of any other investigational agent used during the 30 days prior to Screening.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>On Cerefolin NAC and open-label multivitamin supplement | Other: Cerefolin NAC (a medical food)<br>* Cerefolin NAC one tablet each day<br>|
| Placebo Comparator: 2<br>On placebo and open label multivitamin supplement | Other: Cerefolin NAC placebo<br>* Placebo tablet once a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six Month Blood Levels of Homocysteine, Glutathione, and the Ratio of Aβ42 to Aβ40 (as a Percent of Baseline Levels) After Daily Intake of Cerefolin NAC Plus a Multivitamin Versus a Multivitamin Only | Primary outcome markers were plasma homocysteine (tHcy), glutathione, and the ratio of amyloid proteins, Aβ42 and Aβ40. Plasma tHcy and glutathione were assayed using a high performance liquid chromatography (HPLC) with fluorescence detection method. Enzyme-linked immunosorbent assays (ELISA) were used for Aβ42 (Wako Chemicals USA, Inc., Richmond, VA) and Aβ40 (Invitrogen Corporation, Canarillo, CA) detection. Primary analyses utilized Last Observation Carried Forward (LOCF) to assess the primary biomarker level at 6 months versus baseline. Six month levels in biomarker outcomes were compared using t-tests of the logarithmically transformed values and the antilogarithm was applied to the SDs obtain 95% confidence intervals (95% CIs). A significant difference between treatments was needed for at least one of the primary outcome variables (tHcy, glutathione, or the Aβ42 to Aβ40 ratio) to declare the study positive. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability of Cerefolin NAC and a Multivitamin Versus a Multivitamin Only | Mean study product compliance was measured as the actual number of study product tablets taken as a percent of the maximum study product tablets that could have been taken during the intervention period. | 6 months | 
| Six Month Levels of Inflammation and Oxidative Stress Markers(as a Percent of Baseline Levels) After Daily Treatment With Cerefolin NAC and a Multivitamin or a Multivitamin Only | Outcome measures were 6-month levels of highly sensitive c-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), malondialdehyde, and potential anti-oxidant (PAO)in blood samples as a percent of baseline value. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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memory loss