Cardiovascular Diseases, Coronary Disease, Heart Diseases, Neurologic Manifestations
Conditions
Brief summary
The purpose of this study is to examine the effects of supplemental magnesium on the neurocognitive function of individuals undergoing coronary artery bypass graft (CABG) surgery.
Detailed description
BACKGROUND: Approximately 400,000 individuals undergo heart operations each year and cognitive impairment occurs frequently following surgery. An increasing number of these individuals are elderly and are particularly susceptible to cognitive dysfunction following surgery. Cognitive impairment is most notable in the early stages following heart surgery, but it may persist in some individuals. While many people think cognitive impairment is subtle, transient, or subclinical, perioperative decline is associated with 5-year cognitive deterioration and reduced quality of life. Multiple strategies, both clinical and pharmacological, have been proposed to reduce the central nervous system dysfunction associated with heart surgery. However, most strategies have been unsuccessful, met with limited success, or are unrealistic from a cost or risk-benefit ratio for the majority of people. This study will examine the effectiveness of supplemental magnesium at preventing the cognitive decline associated with heart surgery. DESIGN NARRATIVE: This study will examine the effect of supplemental magnesium on the neurocognitive function of individuals undergoing CABG surgery. The two hypotheses to be tested include the following: 1) therapeutic levels of magnesium reduce post-operative neurocognitive dysfunction after heart surgery; and 2) therapeutic magnesium levels protect quality of life through reduced cognitive dysfunction after heart surgery. This double-blind study will enroll 400 individuals and randomly assign them to either the treatment group, which will receive 100 mg/kg of magnesium, or to the control group. Anesthesia management will be standardized to minimize any impact that anesthesia may have on neurologic or neuropsychologic outcome. Neurocognitive testing will be conducted prior to surgery, and 6 weeks and 1 year following surgery.
Interventions
DRUGMagnesium
100 mg/kg
DRUG0.9% saline
Placebo
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Coronary heart disease
Exclusion criteria
* Early dementia * History of psychiatric illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Function | Measured at baseline and 6 weeks | To characterize cognitive function over time, while minimizing potential redundancy in the cognitive measures, a factor analysis was performed on the cognitive test scores from baseline. We chose a four-factor solution, which represents 4 cognitive domains: verbal memory, abstraction and visuo-spatial orientation (executive function), visual memory and attention and concentration. To quantify overall cognitive function, a baseline cognitive index was first calculated as the mean of the 4 preoperative domain scores. The cognitive index score has a mean of zero and standard deviation of 0.5. Thus, any positive score is above the mean, any negative score is below the mean, and a score of 0.5 represents 1 SD above the mean. A continuous change score was then calculated by subtracting the baseline from the 6-week cognitive index. Negative scores indicate decline and positive scores indicate improvement. |
Countries
United States
Participant flow
Recruitment details
Hospital and preoperative clinic
Participants by arm
| Arm | Count |
|---|---|
| Magnesium 100 mg/kg magnesium | 198 |
| 0.9 % Saline 100 mg/kg 0.9 % saline | 191 |
| Total | 389 |
Baseline characteristics
| Characteristic | 0.9 % Saline | Magnesium | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 117 Participants | 120 Participants | 237 Participants |
| Age, Categorical Between 18 and 65 years | 74 Participants | 78 Participants | 152 Participants |
| Age Continuous | 68.4 years STANDARD_DEVIATION 8 | 68.6 years STANDARD_DEVIATION 8.4 | 68.5 years STANDARD_DEVIATION 8.2 |
| Region of Enrollment United States | 191 participants | 198 participants | 389 participants |
| Sex: Female, Male Female | 66 Participants | 54 Participants | 120 Participants |
| Sex: Female, Male Male | 125 Participants | 144 Participants | 269 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 137 / 198 | 109 / 191 |
| serious Total, serious adverse events | 37 / 198 | 32 / 191 |
Outcome results
Primary
Cognitive Function
To characterize cognitive function over time, while minimizing potential redundancy in the cognitive measures, a factor analysis was performed on the cognitive test scores from baseline. We chose a four-factor solution, which represents 4 cognitive domains: verbal memory, abstraction and visuo-spatial orientation (executive function), visual memory and attention and concentration. To quantify overall cognitive function, a baseline cognitive index was first calculated as the mean of the 4 preoperative domain scores. The cognitive index score has a mean of zero and standard deviation of 0.5. Thus, any positive score is above the mean, any negative score is below the mean, and a score of 0.5 represents 1 SD above the mean. A continuous change score was then calculated by subtracting the baseline from the 6-week cognitive index. Negative scores indicate decline and positive scores indicate improvement.
Time frame: Measured at baseline and 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Magnesium | Cognitive Function | 0.07 Continuous cognitive change score | Standard Deviation 0.28 |
| 0.9 % Saline | Cognitive Function | 0.12 Continuous cognitive change score | Standard Deviation 0.28 |