Study of the Effects of Cerefolin NAC on Inflammation Blood Markers in Older Individuals With Memory Complaints
|Subjective Memory Loss in Older Persons||Other: Cerefolin NAC (a medical food) Other: Cerefolin NAC placebo|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||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|
- 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 [ Time Frame: 6 months ]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.
- Tolerability of Cerefolin NAC and a Multivitamin Versus a Multivitamin Only [ Time Frame: 6 months ]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.
- 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 [ Time Frame: 6 months ]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.
|Study Start Date:||November 2007|
|Study Completion Date:||May 2011|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
On Cerefolin NAC and open-label multivitamin supplement
Other: Cerefolin NAC (a medical food)
Cerefolin NAC one tablet each day
Placebo Comparator: 2
On placebo and open label multivitamin supplement
Other: Cerefolin NAC placebo
Placebo tablet once a day
Study Phase: Exploratory
Indication: Memory Complaints
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.
100 subjects as follows:
- 50 on Cerefolin® NAC + multivitamin; and,
- 50 on Placebo + multivitamin.
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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00597376
|United States, Illinois|
|Rush Alzheimer's Disease Center|
|Chicago, Illinois, United States, 60612|
|Principal Investigator:||Raj C Shah, MD||Rush University Medical Center|