Spinal Cord Injury
Conditions
Keywords
cardiovascular risk
Brief summary
The overall study objectives are to examine whether: 1. Persons with spinal cord injury (SCI) having elevated body mass are at greater cardiovascular disease (CVD) risk for fasting and postprandial lipidemia, glycemia, and vascular inflammation than persons with SCI having 'normal' body mass, and 2. An inexpensive, low-risk, widely-available pharmacotherapy safely reduces CVD risks associated with fasting and postprandial lipidemia, glycemia, and vascular inflammation.
Detailed description
To test Study Objective 1, 'overweight' and 'non-overweight' persons with SCI will be compared at baseline for fasting and postprandial responses. For Study Objective 2, all persons tested for Study Objective 1 will undergo randomization to either 1 month of Salsalate (4.0 g/day) or placebo. An untreated wash-in (1 month) will precede treatment (1 month), and a washout cross-over period (1 month) will follow. The last month will test effects of drug-placebo not examined in month 2. Fasting and postprandial responses will be tested at each time point. Intention-to-treat clinical standards (…as randomized, so analyzed…) and 'last observation carried forward' clinical methods will be adopted. Participants with tetraplegia are sought, as they have fewer exercise options than those with paraplegia and are at greater risk for sedentary lifestyle resulting in CVD, CVD risks, and obesity.
Interventions
DRUGSalsalate 2grams twice a day for 30 days. Then Placebo for 30 days
Participants will undergo randomization to either 1 month of Salsalate (4.0 g/day) or placebo. An untreated wash-in (1 month) will precede treatment (1 month), and a washout cross-over period (1 month) will follow. After the wash-in month participants will receive either Salsalate or the placebo. The last month will test effects of drug-placebo not examined in month 2
DRUGPlacebo twice a day for 30 days. Then Salsalate 2gr BID for 30 days.
Participants will undergo randomization to either 1 month of Salsalate (4.0 g/day) or placebo. An untreated wash-in (1 month) will precede treatment (1 month), and a washout cross-over period (1 month) will follow. After the wash-in month participants will receive either Salsalate or the placebo. The last month will test effects of drug-placebo not examined in month 2.
Sponsors
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* SCI resulting in tetraplegia at C3-C7 * injury for more than one year
Exclusion criteria
* 1\. any recent dietary or other lifestyle changes; * 2\. diabetes or inflammatory medical conditions; * 3\. a pressure ulcer; * 4\. lung or bladder infection; * 5\. undiagnosed illness or fever; * 6\. recent surgery; * 7\. stomach ulcer or a history of stomach upset when taking aspirin or medicines like aspirin, or , * 8\. currently taking medicines used for pain or inflammation (aspirin and non-steroidal anti-inflammatory drugs, corticosteroids), blood vessel diseases (statins or fibric acid derivatives), blood clotting disorders (Coumadin, Plavix), infections (antibiotics), diabetes (Metformin), and burning 'central' pain (voltage regulators).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Area Under the Curve (AUC) for Lipemia (Triglycerides) at Visits 2-3 or 4-5 Depending on Order of Treatment Assignment. | Each visit samples at 0 (immediately post-feeding), and 30,60,90,120,240,360,480 min post-feeding.. | The postprandial lipemia is assessed by the change in the AUC for plasma triglycerides sampled before and after intervention at time points 0 (immediately post-feeding)to 480 min. For peak TG, and TG area under the curve (AUC), treatments (placebo and salsalate) and visits (pre and post treatment) were defined as within-subject's factors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Area Under the Curve (AUC) for Glycemia (Glucose) at Visits 2-3 or 4-5 Depending on Order of Treatment Assignment. | Blood samples for each visit were sampled at 0 (immediately post-feeding), and 30,60,90,120,240,360,480 min post-feeding.. | The postprandial glycemia is assessed by the change in the AUC for plasma glucose sampled before and after intervention at time points of 0 (immediately post-feeding) to 480 min. For peak Glucose, and Glucose area under the curve (AUC), treatments (placebo and salsalate) and visits (pre and post treatment) were defined as within-subject's factors. |
| Change in Area Under the Curve (AUC) for Lipemia (Free Fatty Acids ) at Visits 2-3 or 4-5 Depending on Order of Treatment Assignment. | Each visit sampled at 0 (immediately post-feeding), and 30,60,90,120,240,360,480 min post-feeding.. | The postprandial lipemia is assessed by the change in the AUC for plasma Free fatty acids (FFA)sampled before and after intervention at time points of 0min immediately post feeding to 480 min. For peak FFA area under the curve (AUC), treatments (placebo and salsalate) and visits (pre and post treatment) were defined as within-subject's factors. |
| Change in Fasting Values for Vascular Inflammation IL-6 at Visits 2-3 or 4-5 | Study visit at min -30 (fasting) | The pro-atherogenic inflammatory mediators are assessed by the change in fasting values of Interleukin-6 in plasma concentration Pre and Post intervention at -30 min ( fasting). For fasting values treatments (placebo and salsalate) and visits (pre and post) were defined as within subject's factors. |
Countries
United States
Participant flow
Recruitment details
Participants underwent randomization to either 1 month of Salsalate ( 4.0 grams daily in split doses) or placebo.
Pre-assignment details
An untreated wash-in (1 month) preceded treatment (1 month).A 1 month wash-out between cross-over.
Participants by arm
| Arm | Count |
|---|---|
| Placebo to Salsalate 2gr BID Placebo twice a day for 30 days. Then Salsalate 2gr BID for 30 days.
Placebo twice a day for 30 days. Then Salsalate 2gr BID for 30 days.: Participants will undergo randomization to either 1 month of Salsalate (4.0 g/day) or placebo. An untreated wash-in (1 month) will precede treatment (1 month), and a washout cross-over period (1 month) will follow. After the wash-in month participants will receive either Salsalate or the placebo. The last month will test effects of drug-placebo not examined in month 2. | 10 |
| Salsalate to Placebo 2gr BID Salsalate 2grams twice a day for 30 days. Then Placebo for 30 days.
Salsalate 2grams twice a day for 30 days. Then Placebo for 30 days: Participants will undergo randomization to either 1 month of Salsalate (4.0 g/day) or placebo. An untreated wash-in (1 month) will precede treatment (1 month), and a washout cross-over period (1 month) will follow. After the wash-in month participants will receive either Salsalate or the placebo. The last month will test effects of drug-placebo not examined in month 2 | 8 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Visit 1 Wash-in ( Untreated) | Lost to Follow-up | 2 | 1 |
| Visit 3 - Washout | Adverse Event | 0 | 3 |
| Visit 3 - Washout | Lost to Follow-up | 1 | 0 |
| Visit 4 Crossover | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo to Salsalate 2gr BID | Salsalate to Placebo 2gr BID | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 8 Participants | 18 Participants |
| Age, Continuous | 36 years STANDARD_DEVIATION 10 | 25 years STANDARD_DEVIATION 3 | 33 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 18 | 3 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
Change in Area Under the Curve (AUC) for Lipemia (Triglycerides) at Visits 2-3 or 4-5 Depending on Order of Treatment Assignment.
The postprandial lipemia is assessed by the change in the AUC for plasma triglycerides sampled before and after intervention at time points 0 (immediately post-feeding)to 480 min. For peak TG, and TG area under the curve (AUC), treatments (placebo and salsalate) and visits (pre and post treatment) were defined as within-subject's factors.
Time frame: Each visit samples at 0 (immediately post-feeding), and 30,60,90,120,240,360,480 min post-feeding..
Population: All enrolled participants who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Area Under the Curve (AUC) for Lipemia (Triglycerides) at Visits 2-3 or 4-5 Depending on Order of Treatment Assignment. | -34 mg*min/dL | Standard Deviation 104 |
| Salsalate | Change in Area Under the Curve (AUC) for Lipemia (Triglycerides) at Visits 2-3 or 4-5 Depending on Order of Treatment Assignment. | -62 mg*min/dL | Standard Deviation 136 |
Secondary
Change in Area Under the Curve (AUC) for Glycemia (Glucose) at Visits 2-3 or 4-5 Depending on Order of Treatment Assignment.
The postprandial glycemia is assessed by the change in the AUC for plasma glucose sampled before and after intervention at time points of 0 (immediately post-feeding) to 480 min. For peak Glucose, and Glucose area under the curve (AUC), treatments (placebo and salsalate) and visits (pre and post treatment) were defined as within-subject's factors.
Time frame: Blood samples for each visit were sampled at 0 (immediately post-feeding), and 30,60,90,120,240,360,480 min post-feeding..
Population: All participants who completed treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Area Under the Curve (AUC) for Glycemia (Glucose) at Visits 2-3 or 4-5 Depending on Order of Treatment Assignment. | 1 mg*min/dL | Standard Deviation 15 |
| Salsalate | Change in Area Under the Curve (AUC) for Glycemia (Glucose) at Visits 2-3 or 4-5 Depending on Order of Treatment Assignment. | -8 mg*min/dL | Standard Deviation 20 |
Secondary
Change in Area Under the Curve (AUC) for Lipemia (Free Fatty Acids ) at Visits 2-3 or 4-5 Depending on Order of Treatment Assignment.
The postprandial lipemia is assessed by the change in the AUC for plasma Free fatty acids (FFA)sampled before and after intervention at time points of 0min immediately post feeding to 480 min. For peak FFA area under the curve (AUC), treatments (placebo and salsalate) and visits (pre and post treatment) were defined as within-subject's factors.
Time frame: Each visit sampled at 0 (immediately post-feeding), and 30,60,90,120,240,360,480 min post-feeding..
Population: All enrolled participants who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Area Under the Curve (AUC) for Lipemia (Free Fatty Acids ) at Visits 2-3 or 4-5 Depending on Order of Treatment Assignment. | 8 mg*min/dL | Standard Deviation 193 |
| Salsalate | Change in Area Under the Curve (AUC) for Lipemia (Free Fatty Acids ) at Visits 2-3 or 4-5 Depending on Order of Treatment Assignment. | -111 mg*min/dL | Standard Deviation 174 |
Secondary
Change in Fasting Values for Vascular Inflammation IL-6 at Visits 2-3 or 4-5
The pro-atherogenic inflammatory mediators are assessed by the change in fasting values of Interleukin-6 in plasma concentration Pre and Post intervention at -30 min ( fasting). For fasting values treatments (placebo and salsalate) and visits (pre and post) were defined as within subject's factors.
Time frame: Study visit at min -30 (fasting)
Population: All enrolled participants who completed the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Fasting Values for Vascular Inflammation IL-6 at Visits 2-3 or 4-5 | Pre-Intervention | 0.48 mg/dL | Standard Deviation 0.35 |
| Placebo | Change in Fasting Values for Vascular Inflammation IL-6 at Visits 2-3 or 4-5 | Post-Intervention | 0.50 mg/dL | Standard Deviation 0.49 |
| Salsalate | Change in Fasting Values for Vascular Inflammation IL-6 at Visits 2-3 or 4-5 | Pre-Intervention | 0.51 mg/dL | Standard Deviation 0.55 |
| Salsalate | Change in Fasting Values for Vascular Inflammation IL-6 at Visits 2-3 or 4-5 | Post-Intervention | 0.19 mg/dL | Standard Deviation 0.53 |