Inflammation and Vascular Function in Atherosclerosis

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00760019
• Collaborator: (none)
• Enrollment: 58
• Location: 1
• Arms: 2
• Duration (Months): 66
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether reducing inflammation in blood vessels with an aspirin-like drug called salsalate will improve blood vessel function.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis	Drug: salsalate; Drug: placebo	Phase 2/Phase 3

Detailed Description

To test the hypothesis that inhibition of I [kappa] B kinase [beta] (IĸKβ), an inflammatory mediator, by high dose salsalate, will restore insulin-mediated endothelium-dependent vasodilation in subjects with atherosclerosis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Inflammation and Vascular Function in Atherosclerosis
• Study Start Date: Aug 1, 2005
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Salsalate first, then Placebo In this crossover study, this group was randomly allocated therapy with salsalate first, a 4 week washout, then 4 weeks of placebo therapy in a double-blinded fashion.	Drug: salsalate; 1.5 grams orally 3 times daily; Other Names: Disalcid
Placebo Comparator: Placebo first, then Salsalate In this crossover study, this group was randomly allocated therapy with placebo first, a 4 week washout, then 4 weeks of salsalate therapy in a double-blinded fashion.	Drug: placebo; matching placebo

Outcome Measures

Primary Outcome Measures

1. Flow-mediated, Endothelium-dependent Vasodilation [Upon completion of 4 weeks of salsalate and placebo treatment]

   Flow-mediated, endothelium-dependent vasodilation (percentage increase in brachial artery diameter after a 5 minute ischemic stimulus) measured at the end of placebo treatment and end of salsalate treatment were compared.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Non-smoking adult subjects with known atherosclerosis

Exclusion Criteria:

• Uncontrolled hypertension (> 140/90 mmHg)

• Untreated hypercholesterolemia (LDL > 160 mg/dL)

• Diabetes mellitus

• Alanine Aminotransferase > 150

• Creatinine > 1.4 mg/dL

• Concommitant use of warfarin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Brigham and Women's Hospital

Investigators

• Principal Investigator: Joshua A. Beckman, M.D., Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joshua A. Beckman, MD, MD, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT00760019
• Other Study ID Numbers: 2005P-001406; NCT00762827
• First Posted: Sep 25, 2008
• Last Update Posted: May 16, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Joshua A. Beckman, MD, MD, Brigham and Women's Hospital: vascular inflammation; endothelium-dependent flow-mediated blood vessel function
• Additional relevant MeSH terms: Atherosclerosis; Inflammation; Salicylsalicylic acid

Study Results

Participant Flow

Arm/Group Title	Atherosclerosis/Metabolic Syndrome: Salsalate First, Then Plac	Atherosclerosis/Metabolic Syndrome: Placebo First, Then Salsal	Healthy Subjects: Salsalate First, Then Placebo	Healthy Subjects: Placebo First, Then Salsalate
Arm/Group Description	Subjects with either Metabolic Syndrome/Atherosclerosis received either 4.5 g/day salsalate for 4 weeks, washout for 4 weeks, and matching placebo for 4 weeks.	Subjects with either Metabolic Syndrome/Atherosclerosis received placebo for 4 weeks, washout for 4 weeks, and 4.5 g/day salsalate for 4 weeks.	Healthy subjects received either 4.5 g/day salsalate for 4 weeks, washout for 4 weeks, and matching placebo for 4 weeks.	Healthy subjects received placebo for 4 weeks, washout for 4 weeks, and 4.5 g/day salsalate for 4 weeks.
Period Title: Overall Study
STARTED	15	15	14	14
COMPLETED	15	15	14	14
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Atherosclerosis or Metabolic Syndrome	Healthy	Total
Arm/Group Description	Participant flow is identical to that of NCT00762827 ("The Impact of Reducing Inflammation on Vascular Function in the Metabolic Syndrome"): The study arms reflect the randomized, placebo-controlled, double-blinded crossover design of the study. In this arm, individuals with either Metabolic Syndrome or Atherosclerosis received either 4.5 g/day salsalate or matching placebo for a 4-week long period. After a 4-week washout interval, these individuals crossed over and received either the salsalate or the placebo (whichever they did not receive in the first study period) for another 4 weeks.	Participant flow is identical to that of NCT00762827 ("The Impact of Reducing Inflammation on Vascular Function in the Metabolic Syndrome"): The study arms reflect the randomized, placebo-controlled, double-blinded crossover design of the study. In this control arm, healthy individuals received either 4.5 g/day salsalate or matching placebo for a 4-week long period. After a 4-week washout interval, these individuals crossed over and received either the salsalate or the placebo (whichever they did not receive in the first study period) for another 4 weeks.	Total of all reporting groups
Overall Participants	30	28	58
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60 (9)	52 (13)	56 (11)
Sex: Female, Male (Count of Participants)
Female	8 26.7%	12 42.9%	20 34.5%
Male	22 73.3%	16 57.1%	38 65.5%

Outcome Measures

1. Primary Outcome

Title	Flow-mediated, Endothelium-dependent Vasodilation
Description	Flow-mediated, endothelium-dependent vasodilation (percentage increase in brachial artery diameter after a 5 minute ischemic stimulus) measured at the end of placebo treatment and end of salsalate treatment were compared.
Time Frame	Upon completion of 4 weeks of salsalate and placebo treatment

Outcome Measure Data

Analysis Population Description

The ultrasound data for two subjects was inadequate for analysis. This determination was made prior to unblinding. The data for these two subjects were discarded, leaving 56 subjects for analysis.

Arm/Group Title	Salsalate	Placebo
Arm/Group Description	Outcomes were measured at the end of each 4-week study period. Here, median flow-mediated, endothelium-dependent vasodilation after 4 weeks of 4.5 g/day salsalate is compared with median FMD after 4 weeks of matching placebo. Data represent all subjects: those with atherosclerosis/metabolic syndrome as well as healthy controls.	Outcomes were measured at the end of each 4-week study period. Here, median flow-mediated, endothelium-dependent vasodilation after 4 weeks of 4.5 g/day salsalate is compared with median FMD after 4 weeks of matching placebo. Data represent all subjects: those with atherosclerosis/metabolic syndrome as well as healthy controls.
Measure Participants	56	56
Median (Inter-Quartile Range) [percentage vasodilation]	6.8	8.7

Adverse Events

Arm/Group Title	Salsalate		Placebo
Arm/Group Description	Adverse Event Data represent all subjects: those with atherosclerosis/metabolic syndrome as well as healthy controls that received Salsalate		Adverse Event Data represent all subjects: those with atherosclerosis/metabolic syndrome as well as healthy controls that received Placebo
All Cause Mortality
	Salsalate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/58 (0%)
Serious Adverse Events
	Salsalate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/58 (0%)		0/58 (0%)
Other (Not Including Serious) Adverse Events
	Salsalate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/58 (10.3%)		0/58 (0%)
Ear and labyrinth disorders
Tinnitus	6/58 (10.3%)	6	0/58 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.