Effects of Salsalate on Prandial-Induced Vascular Inflammation After Spinal Cord Injury (SCI)

Effects of Salsalate on Prandial-Induced Vascular Inflammation After SCI

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.

Study Overview

• Status: Completed
• Conditions: Spinal Cord Injury
• Intervention / Treatment: Drug: Salsalate 2grams twice a day for 30 days. Then Placebo for 30 days; Drug: Placebo twice a day for 30 days. Then Salsalate 2gr BID for 30 days.

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • The Miami Project to Cure Paralysis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo to Salsalate 2gr BID; Placebo twice a day for 30 days. Then Salsalate 2gr BID for 30 days.	Drug: 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; Drug: 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.
Experimental: Salsalate 2gr BID to placebo; Salsalate 2grams twice a day for 30 days. Then Placebo for 30 days.	Drug: 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; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Each visit samples at 0 (immediately post-feeding), and 30,60,90,120,240,360,480 min post-feeding..

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Blood samples for each visit were sampled at 0 (immediately post-feeding), and 30,60,90,120,240,360,480 min post-feeding..
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.	Each visit sampled at 0 (immediately post-feeding), and 30,60,90,120,240,360,480 min post-feeding..
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.	Study visit at min -30 (fasting)

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Mark S Nash, PhD, University of Miami Miller School of Medicine, The Miami Project to Cure Paralysis

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: September 8, 2010
• First Submitted That Met QC Criteria: September 14, 2010
• First Posted (Estimate): September 15, 2010

Study Record Updates

• Last Update Posted (Estimate): June 10, 2015
• Last Update Submitted That Met QC Criteria: June 8, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: cardiovascular risk
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Inflammation; Spinal Cord Injuries; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Salicylsalicylic acid; Sodium Salicylate
• Other Study ID Numbers: 20090361; TMP-MN-004 (Other Identifier: Clinicaltrials.gov)