Trial Outcomes & Findings for Study of the Effects of Cerefolin NAC on Inflammation Blood Markers in Older Individuals With Memory Complaints (NCT NCT00597376)
NCT ID: NCT00597376
Last Updated: 2013-05-23
Results Overview
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.
COMPLETED
NA
104 participants
6 months
2013-05-23
Participant Flow
Between March 2008 and September 2009, persons expressing study interest at community presentations or at the Rush Memory Clinic were contacted. Of 524 persons expressing interest, 400 were excluded before consenting for having excluding clinical diagnoses(227), participation refusal (119), and other exclusions medication (54).
Consented participants underwent a screening evaluation to ensure inclusion criteria were met prior to study treatment assignment and one month run-in treatment with a multivitamin only. Of 124 consented individuals, 20 discontinued prior to randomization due to new medical conditions (9), declining participation (5), and for other reasons (6).
Participant milestones
| Measure |
Cerefolin NAC + Multivitamin
On Cerefolin NAC and open-label multivitamin supplement
Cerefolin NAC (a medical food) : Cerefolin NAC one tablet each day
|
Cerefolin NAC Placebo + Multivitamin
On placebo and open label multivitamin supplement
Cerefolin NAC placebo : Placebo tablet once a day
|
|---|---|---|
|
Overall Study
STARTED
|
51
|
53
|
|
Overall Study
COMPLETED
|
43
|
49
|
|
Overall Study
NOT COMPLETED
|
8
|
4
|
Reasons for withdrawal
| Measure |
Cerefolin NAC + Multivitamin
On Cerefolin NAC and open-label multivitamin supplement
Cerefolin NAC (a medical food) : Cerefolin NAC one tablet each day
|
Cerefolin NAC Placebo + Multivitamin
On placebo and open label multivitamin supplement
Cerefolin NAC placebo : Placebo tablet once a day
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
4
|
3
|
|
Overall Study
Adverse Event
|
4
|
1
|
Baseline Characteristics
Study of the Effects of Cerefolin NAC on Inflammation Blood Markers in Older Individuals With Memory Complaints
Baseline characteristics by cohort
| Measure |
Cerefolin NAC + Multivitamin
n=51 Participants
On Cerefolin NAC and open-label multivitamin supplement
Cerefolin NAC (a medical food) : Cerefolin NAC one tablet each day
|
Cerefolin NAC Placebo + Multivitamin
n=53 Participants
On placebo and open label multivitamin supplement
Cerefolin NAC placebo : Placebo tablet once a day
|
Total
n=104 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
80.9 years
STANDARD_DEVIATION 6.6 • n=5 Participants
|
79.4 years
STANDARD_DEVIATION 8.7 • n=7 Participants
|
80.1 years
STANDARD_DEVIATION 7.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
46 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
88 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
51 participants
n=5 Participants
|
53 participants
n=7 Participants
|
104 participants
n=5 Participants
|
|
Education Level
|
15 years
STANDARD_DEVIATION 3 • n=5 Participants
|
15 years
STANDARD_DEVIATION 3 • n=7 Participants
|
15 years
STANDARD_DEVIATION 3 • n=5 Participants
|
|
total plasma homocysteine
|
8.35 micromol/L
STANDARD_DEVIATION 1.32 • n=5 Participants
|
8.10 micromol/L
STANDARD_DEVIATION 1.33 • n=7 Participants
|
8.22 micromol/L
STANDARD_DEVIATION 1.33 • n=5 Participants
|
|
glutathione
|
4.01 micromol/L
STANDARD_DEVIATION 1.67 • n=5 Participants
|
4.02 micromol/L
STANDARD_DEVIATION 1.59 • n=7 Participants
|
4.02 micromol/L
STANDARD_DEVIATION 1.63 • n=5 Participants
|
|
ratio of amyloid beta 1-42 to 1-40
|
0.027 pmol/L:pmol/L
STANDARD_DEVIATION 1.73 • n=5 Participants
|
0.034 pmol/L:pmol/L
STANDARD_DEVIATION 1.81 • n=7 Participants
|
0.031 pmol/L:pmol/L
STANDARD_DEVIATION 1.77 • n=5 Participants
|
|
highly sensitive c-Reactive Protein
|
0.20 mg/mL
STANDARD_DEVIATION 18.93 • n=5 Participants
|
0.23 mg/mL
STANDARD_DEVIATION 22.37 • n=7 Participants
|
0.22 mg/mL
STANDARD_DEVIATION 20.68 • n=5 Participants
|
|
tumor necrosis factor alpha
|
1.45 pg/mL
STANDARD_DEVIATION 1.61 • n=5 Participants
|
1.37 pg/mL
STANDARD_DEVIATION 1.53 • n=7 Participants
|
1.41 pg/mL
STANDARD_DEVIATION 1.57 • n=5 Participants
|
|
interleukin-6
|
2.12 pg/mL
STANDARD_DEVIATION 1.98 • n=5 Participants
|
2.12 pg/mL
STANDARD_DEVIATION 2.35 • n=7 Participants
|
2.12 pg/mL
STANDARD_DEVIATION 2.17 • n=5 Participants
|
|
malondialdehyde
|
0.90 micromol/L
STANDARD_DEVIATION 1.67 • n=5 Participants
|
0.93 micromol/L
STANDARD_DEVIATION 1.75 • n=7 Participants
|
0.92 micromol/L
STANDARD_DEVIATION 1.71 • n=5 Participants
|
|
potential anti-oxidant (PAO)
|
979 micromol/L
STANDARD_DEVIATION 2 • n=5 Participants
|
1016 micromol/L
STANDARD_DEVIATION 2 • n=7 Participants
|
997 micromol/L
STANDARD_DEVIATION 2 • n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: The Intent-to-Treat (ITT) cohort included randomized subjects taking at least one study treatment dose. Primary analyses utilized Last Observation Carried Forward (LOCF) to assess 6 month levels in the primary biomarkers. 2-sided, t-test p-value for group differences was only significant (\<0.05) for 6-month homocysteine level.
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.
Outcome measures
| Measure |
Cerefolin NAC + Multivitamin
n=51 Participants
On Cerefolin NAC and open-label multivitamin supplement
|
Cerefolin NAC Placebo + Multivitamin
n=53 Participants
On placebo and open-label multivitamin supplement
|
|---|---|---|
|
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
6-Month Homocysteine Level
|
71 percent of baseline level
Interval 66.0 to 77.0
|
101 percent of baseline level
Interval 96.0 to 107.0
|
|
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
6-Month Glutathione Level
|
115 percent of baseline level
Interval 101.0 to 129.0
|
101 percent of baseline level
Interval 85.0 to 117.0
|
|
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
6-Month AB42/AB40 Ratio
|
101 percent of baseline level
Interval 92.0 to 110.0
|
104 percent of baseline level
Interval 97.0 to 108.0
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: All participants in Intent-to-Treat cohort were included.
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.
Outcome measures
| Measure |
Cerefolin NAC + Multivitamin
n=51 Participants
On Cerefolin NAC and open-label multivitamin supplement
|
Cerefolin NAC Placebo + Multivitamin
n=53 Participants
On placebo and open-label multivitamin supplement
|
|---|---|---|
|
Tolerability of Cerefolin NAC and a Multivitamin Versus a Multivitamin Only
|
88 percent of study drug taken
Standard Error 15
|
88 percent of study drug taken
Standard Error 21
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: All participants in Intent-to-Treat were included with last observation carried forward.
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.
Outcome measures
| Measure |
Cerefolin NAC + Multivitamin
n=51 Participants
On Cerefolin NAC and open-label multivitamin supplement
|
Cerefolin NAC Placebo + Multivitamin
n=53 Participants
On placebo and open-label multivitamin supplement
|
|---|---|---|
|
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
6-month TNF-alpha Level
|
99 percent of baseline level
Interval 93.0 to 106.0
|
108 percent of baseline level
Interval 98.0 to 118.0
|
|
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
6-month hs-CRP Level
|
110 percent of baseline level
Interval 51.0 to 238.0
|
111 percent of baseline level
Interval 53.0 to 234.0
|
|
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
6-month IL-6 Level
|
114 percent of baseline level
Interval 97.0 to 134.0
|
105 percent of baseline level
Interval 88.0 to 125.0
|
|
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
6-month Malondialdehyde Level
|
93 percent of baseline level
Interval 83.0 to 104.0
|
90 percent of baseline level
Interval 79.0 to 102.0
|
|
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
6-month PAO Level
|
109 percent of baseline level
Interval 96.0 to 123.0
|
115 percent of baseline level
Interval 100.0 to 131.0
|
Adverse Events
Cerefolin NAC + Multivitamin
Cerefolin NAC Placebo + Multivitamin
Serious adverse events
| Measure |
Cerefolin NAC + Multivitamin
n=51 participants at risk
On Cerefolin NAC and open-label multivitamin supplement
|
Cerefolin NAC Placebo + Multivitamin
n=53 participants at risk
On placebo and open-label multivitamin supplement
|
|---|---|---|
|
Cardiac disorders
Cardiac disorders
|
5.9%
3/51 • Number of events 3
|
5.7%
3/53 • Number of events 3
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
3.9%
2/51 • Number of events 2
|
0.00%
0/53
|
|
General disorders
General Disorders
|
3.9%
2/51 • Number of events 2
|
3.8%
2/53 • Number of events 2
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders
|
2.0%
1/51 • Number of events 1
|
0.00%
0/53
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders
|
2.0%
1/51 • Number of events 1
|
1.9%
1/53 • Number of events 1
|
|
Nervous system disorders
Nervous system disorders
|
0.00%
0/51
|
1.9%
1/53 • Number of events 1
|
|
Renal and urinary disorders
Renal and urinary disorders
|
5.9%
3/51 • Number of events 3
|
1.9%
1/53 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
2.0%
1/51 • Number of events 1
|
0.00%
0/53
|
Other adverse events
| Measure |
Cerefolin NAC + Multivitamin
n=51 participants at risk
On Cerefolin NAC and open-label multivitamin supplement
|
Cerefolin NAC Placebo + Multivitamin
n=53 participants at risk
On placebo and open-label multivitamin supplement
|
|---|---|---|
|
Cardiac disorders
Cardiac disorders
|
2.0%
1/51 • Number of events 1
|
3.8%
2/53 • Number of events 3
|
|
Eye disorders
Eye disorders
|
2.0%
1/51 • Number of events 1
|
3.8%
2/53 • Number of events 2
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
11.8%
6/51 • Number of events 6
|
5.7%
3/53 • Number of events 4
|
|
General disorders
General disorders
|
7.8%
4/51 • Number of events 4
|
9.4%
5/53 • Number of events 7
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders
|
2.0%
1/51 • Number of events 1
|
3.8%
2/53 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders
|
9.8%
5/51 • Number of events 6
|
11.3%
6/53 • Number of events 7
|
|
Nervous system disorders
Nervous system disorders
|
3.9%
2/51 • Number of events 2
|
9.4%
5/53 • Number of events 5
|
|
Renal and urinary disorders
Renal and urinary disorders
|
2.0%
1/51 • Number of events 1
|
3.8%
2/53 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
11.8%
6/51 • Number of events 7
|
7.5%
4/53 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
|
7.8%
4/51 • Number of events 4
|
9.4%
5/53 • Number of events 5
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place