Cardiovascular Inflammation Reduction Trial - Inflammation Imaging Study (CIRT)

• ClinicalTrials.gov Identifier: NCT02576067
• Recruitment Status: Completed
• First Posted: October 15, 2015
• Results First Posted: April 20, 2020
• Last Update Posted: April 20, 2020
• Sponsor: Icahn School of Medicine at Mount Sinai
• Collaborators: Brigham and Women's Hospital; Massachusetts General Hospital; Unity Health Toronto; National Institutes of Health (NIH); National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Zahi Fayad, Icahn School of Medicine at Mount Sinai

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Conditions: Vascular Inflammation; Atherosclerotic Cardiovascular Disease
• Interventions: Drug: Low dose methotrexate; Drug: Placebo
• Enrollment: 123

Participant Flow

Recruitment Details	Participants enrolled period from Dec 2015 to April 2018
Pre-assignment Details

Arm/Group Title	Low Dose Methotrexate	Placebo
Arm/Group Description	Low dose methotrexate - average dose of 15-20 mg po/weekly. will additionally receive 1 mg daily oral folate.	matching placebo
Period Title: Overall Study
Started	60	63
Completed	26	27
Not Completed	34	36
Reason Not Completed
Death	0	1
Lack of Efficacy	1	0
Lost to Follow-up	11	0
Withdrawal by Subject	11	2
study closure of main CIRT trial)	0	8
not randomized, failed run-in	7	0
screen failure/ re-enrolled	0	25
Physician Decision	4	0

Baseline Characteristics

Arm/Group Title		Low Dose Methotrexate	Placebo	Total
Arm/Group Description		Low dose methotrexate - average dose of 15-20 mg po/weekly. will additionally receive 1 mg daily oral folate.	matching placebo	Total of all reporting groups
Overall Number of Baseline Participants		26	27	53
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	26 participants	27 participants	53 participants
		63; (61 to 67)	65; (59 to 71)	64; (59 to 71)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants	27 participants	53 participants
	Female	4 15.4%	3 11.1%	7 13.2%
	Male	22 84.6%	24 88.9%	46 86.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants	27 participants	53 participants
	Hispanic or Latino	3 11.5%	4 14.8%	7 13.2%
	Not Hispanic or Latino	23 88.5%	23 85.2%	46 86.8%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants	27 participants	53 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	5 19.2%	3 11.1%	8 15.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 7.7%	4 14.8%	6 11.3%
	White	18 69.2%	20 74.1%	38 71.7%
	More than one race	1 3.8%	0 0.0%	1 1.9%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
hs-CRP; Median (Inter-Quartile Range); Unit of measure: mg/L
	Number Analyzed	26 participants	27 participants	53 participants
		1.4; (0.7 to 2.1)	1.1; (0.7 to 2.1)	1.3; (0.7 to 2.1)
Total Cholesterol; Median (Inter-Quartile Range); Unit of measure: mg/dL
	Number Analyzed	26 participants	27 participants	53 participants
		138.1; (108 to 160)	131; (112 to 158)	134; (108 to 160)
LDL cholesterol; Median (Full Range); Unit of measure: mg/dL
	Number Analyzed	26 participants	27 participants	53 participants
		63; (49 to 84)	66; (45.2 to 82)	64; (45 to 84)
HDL cholesterol; Median (Full Range); Unit of measure: mg/dL
	Number Analyzed	26 participants	27 participants	53 participants
		42.5; (38 to 50)	40; (36.3 to 47)	41.5; (36 to 50)
MDS TBR Index Vessel [1]; Median (Inter-Quartile Range); Unit of measure: Ratio
	Number Analyzed	26 participants	27 participants	53 participants
		2.46; (2.15 to 2.77)	2.41; (2.06 to 2.75)	2.44; (2.06 to 2.77)
		[1] Measure Description: Most Diseased Segment (MDS) Target to Background (TBR) Index Vessel
TMNMX MDS [1]; Median (Full Range); Unit of measure: Ratio	Number Analyzed	26 participants	27 participants	53 participants
LCC - left common carotid		2.04; (1.89 to 2.29)	2.12; (1.85 to 2.46)	2.08; (1.85 to 2.46)
RCC - right common carotid		2.12; (2.04 to 2.48)	2.13; (1.99 to 2.36)	2.12; (1.99 to 2.48)
ATA - ascending thoracic aorta		2.45; (2.08 to 2.72)	2.22; (1.97 to 2.71)	2.34; (1.97 to 2.72)
		[1] Measure Description: TMNMX: TBR Mean of the Max MDS
TMNMX [1]; Median (Inter-Quartile Range); Unit of measure: Ratio	Number Analyzed	26 participants	27 participants	53 participants
Combined Carotid		1.93; (1.75 to 2.22)	1.93; (1.77 to 2.24)	1.93; (1.75 to 2.24)
ATA		2.34; (1.98 to 2.53)	2.12; (1.92 to 2.58)	2.23; (1.92 to 2.58)
		[1] Measure Description: TMNMX: TBR Mean of the Max
SMNMX [1]; Median (Full Range); Unit of measure: Ratio	Number Analyzed	26 participants	27 participants	53 participants
Combined Carotid		1.82; (1.63 to 2.20)	1.78; (1.52 to 1.95)	1.80; (1.52 to 2.20)
ATA		2.26; (1.95 to 2.53)	2.24; (2.04 to 2.46)	2.25; (1.95 to 2.53)
		[1] Measure Description: Standardized uptake value mean of the maximum

Outcome Measures

1. Primary Outcome

Title	Change in Arterial Inflammation
Description	Change in arterial inflammation - The relative change at 8 months as compared to baseline in arterial inflammation as measured by the most diseased segment (MDS) of the index vessel. The MDS is defined as the 1.5 cm segment within the carotid artery (right or left carotid) that demonstrates the highest PET/CT activity, and is calculated as a mean of maximum TBR values derived from 3 contiguous axial segments. The index vessel in turn is defined as the vessel (either aorta, right, or left carotid) with the greatest mean TBR at baseline. (MDS TBR Index Vessel)
Time Frame	baseline and 8 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose Methotrexate	Placebo
Arm/Group Description:	Low dose methotrexate - average dose of 15-20 mg po/weekly. will additionally receive 1 mg daily oral folate.	matching placebo
Overall Number of Participants Analyzed	26	27
Median (Inter-Quartile Range); Unit of Measure: percent change
	0.03; (-0.19 to 0.30)	0.20; (-0.06 to 0.42)

2. Secondary Outcome

Title	Change in Max Target-to-background (TBR)
Description	Change in max target-to-background (TBR) - The mean of max TBR within the carotid arteries as an average of the slices from the left and right carotid) at follow up imaging as compared to baseline.
Time Frame	baseline and 8 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose Methotrexate	Placebo
Arm/Group Description:	Low dose methotrexate - average dose of 15-20 mg po/weekly. will additionally receive 1 mg daily oral folate.	matching placebo
Overall Number of Participants Analyzed	26	27
Median (Inter-Quartile Range); Unit of Measure: ratio
	0.06; (-0.08 to 0.21)	0.02; (-0.20 to 0.15)

3. Secondary Outcome

Title	Change in Max TBR Within the Carotid Arteries
Description	Change in max target-to-background (TBR) - The mean of max TBR within the carotid arteries as an average of the slices from the left and right carotid)
Time Frame	baseline and 8 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose Methotrexate	Placebo
Arm/Group Description:	Low dose methotrexate - average dose of 15-20 mg po/weekly. will additionally receive 1 mg daily oral folate.	matching placebo
Overall Number of Participants Analyzed	26	27
Median (Inter-Quartile Range); Unit of Measure: ratio
	-0.04; (-0.29 to 0.12)	0.06; (-0.14 to 0.20)

Adverse Events

Time Frame	8 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Low Dose Methotrexate	Placebo
Arm/Group Description	Low dose methotrexate - average dose of 15-20 mg po/weekly. will additionally receive 1 mg daily oral folate.	matching placebo
All-Cause Mortality
	Low Dose Methotrexate	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/60 (1.67%)	1/63 (1.59%)
Serious Adverse Events
	Low Dose Methotrexate	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/60 (0.00%)	0/63 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Low Dose Methotrexate	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/60 (1.67%)	1/63 (1.59%)
Investigations
Missinjected dose (isotope) † 1	1/60 (1.67%)	1/63 (1.59%)
1 Term from vocabulary, MedDRA (Unspecified); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

Results Point of Contact

• Name/Title: Zahi Fayad, PhD
• Organization: Icahn School of Medicine at Mount Sinai
• Phone: 212-824-8471
• EMail: zahi.fayad@mssm.edu

• Responsible Party: Zahi Fayad, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT02576067
• Other Study ID Numbers: GCO 14-1382; 1R01HL128056-01A1 ( U.S. NIH Grant/Contract )
• First Submitted: October 13, 2015
• First Posted: October 15, 2015
• Results First Submitted: March 27, 2020
• Results First Posted: April 20, 2020
• Last Update Posted: April 20, 2020