CTSI-PLACE: A Prospective, Longitudinal Study of Endothelial Function in HIV/HCV Coinfected Subjects

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT02597790
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 87
• Location: 1
• Duration (Months): 75
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The CTSI-PLACE Study is a study for men and women with HIV/hepatitis C co-infection or HIV only. The study looks at the impact of having hepatitis C virus in addition to HIV on risk for cardiovascular disease. Participants will undergo non-invasive assessment of cardiovascular disease risk through measurements of endothelial function and blood biomarkers at baseline and 1 year (or 4 weeks and 24 weeks after end of HCV treatment for those that undergo HCV treatment during study follow-up).

Condition or Disease	Intervention/Treatment	Phase
HIV; Hepatitis C

Study Design

• Study Type: Observational
• Actual Enrollment: 87 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Clinical and Translational Science Institute Prospective Longitudinal Assessment of Coinfected Subjects With HIV/Hepatitis C for Endothelial Function Study
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Jan 1, 2019
• Actual Study Completion Date: Jan 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Group A (HIV/HCV coinfected)
Group B (HIV monoinfected)

Outcome Measures

Primary Outcome Measures

1. Reactive Hyperemia Index (RHI) by Peripheral Arterial Tonometry (PAT) [Baseline]

   Ratio of the average pulse wave amplitude (PWA) over a 1 minute interval starting 1 minute following cuff release to the pre-occlusion PWA (average over 3.5 minutes pre-cuff inflation)

Secondary Outcome Measures

1. Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163) [Baseline]

   Serum hsCRP

2. Reactive Hyperemia Index (RHI) [Week 52]

   Ratio of the average pulse wave amplitude (PWA) over a 1 minute interval starting 1 minute following cuff release to the pre-occlusion PWA (average over 3.5 minutes pre-cuff inflation)

3. Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163) [Week 52]

   Serum hsCRP

4. Insulin Resistance by HOMA-IR [Baseline]

   fasting insulin (μU/mL) x fasting glucose (mg/dl) / 405

5. Insulin Resistance by HOMA-IR [Week 52]

   fasting insulin (μU/mL) x fasting glucose (mg/dl) / 405

6. Framingham Risk Score (FRS), 10-year Risk (%) [Baseline]

   Estimate of 10-year risk for developing coronary heart disease (CHD), calculated as described in ATP III Executive Summary, JAMA, May 16, 2001-Vol 285, No. 19. Range of values is <1 to >/= 30% Higher risk % is worse predicted outcome.

7. Framingham Risk Score (FRS), 10-year Risk (%) [Week 52]

   Estimate of 10-year risk for developing coronary heart disease (CHD), calculated as described in ATP III Executive Summary, JAMA, May 16, 2001-Vol 285, No. 19. Range of values is <1 to >/= 30% Higher risk % is worse predicted outcome.

8. Change in RHI [Baseline to Week 52]

9. Change in Level of Each Soluble Biomarker (Components of Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163) [Baseline to Week 52]

   Change in serum hsCRP level

10. Change in HOMA-IR [Baseline to Week 52]

11. Change in Framingham Risk Score (10-year Risk, %) [Baseline to Week 52]

    Change in estimated 10-year risk (% risk) for developing coronary heart disease (CHD). Positive value indicates increase in estimated 10-year risk for CHD from baseline to Week 52. Negative value indicates decrease in estimated 10-year risk for CHD from baseline to Week 52.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

1. Men and women ≥ 18 years

2. Hepatitis C negative or chronic hepatitis C infection

3. Chronic HIV infection

4. CD4+ T-cell count > 200 cells/mm3

5. Plasma HIV-1 RNA < 50 copies/mL

6. On continuous and stable ART for at least 12 weeks

7. Ability and willingness to provide written informed consent.

Exclusion Criteria

1. Known cardiovascular disease

2. Diabetes requiring insulin therapy or hemoglobin A1c > 8%

3. Inability to conform to requirements for PAT testing

4. Decompensated liver disease

5. Other known causes of significant liver disease

6. Serious illness including acute liver-related disease and malignancy requiring systemic treatment or hospitalization within 12 weeks prior to study entry

7. Presence of active or acute AIDS-defining opportunistic infections (OIs) within 12 weeks prior to study entry

8. History of major organ transplantation with an existing functional graft and on immunosuppressive therapy

9. History of known vascular or autoimmune disease

10. Pregnancy

11. HCV treatment (any approved or investigational agents) within 24 weeks prior to study entry

12. Use of immune-based therapies or systemic corticosteroids within 12 weeks prior to study entry

13. Advanced renal insufficiency as defined by glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 or treatment by dialysis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA CARE Center	Los Angeles	California	United States	90025

Sponsors and Collaborators

• University of California, Los Angeles
• Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Kara W. Chew, M.D., M.S., University of California, Los Angeles

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 22, 2015

More Information

Publications

None provided.

• Responsible Party: Kara Chew, Assistant Clinical Professor, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT02597790
• Other Study ID Numbers: 12-001792 (CTSI-PLACE); N/A (Parent P30AI028697); N/A (Parent UL1TR000124); 52767
• First Posted: Nov 5, 2015
• Last Update Posted: Jan 20, 2022
• Last Verified: Dec 1, 2021

• Keywords provided by Kara Chew, Assistant Clinical Professor, University of California, Los Angeles: endothelial function; cardiovascular risk; HIV; Hepatitis C; metabolic disease; inflammation
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis

Study Results

Participant Flow

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)
Arm/Group Description	HIV+, HCV viremic at study entry	HIV+, HCV negative at study entry
Period Title: Overall Study
STARTED	45	41
COMPLETED	36	29
NOT COMPLETED	9	12

Baseline Characteristics

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)	Total
Arm/Group Description	HIV+, HCV viremic at study entry	HIV+, HCV negative at study entry	Total of all reporting groups
Overall Participants	45	41	86
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	52	52	52
Sex/Gender, Customized (Count of Participants)
Men	38 84.4%	35 85.4%	73 84.9%
Women	4 8.9%	4 9.8%	8 9.3%
Transgender women	3 6.7%	2 4.9%	5 5.8%
Race/Ethnicity, Customized (Count of Participants)
Black Non-Hispanic	17 37.8%	10 24.4%	27 31.4%
White Non-Hispanic	9 20%	8 19.5%	17 19.8%
Hispanic	17 37.8%	20 48.8%	37 43%
Other	2 4.4%	3 7.3%	5 5.8%
Body mass index (kg/m2) (kg/m2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m2]	27.6	26.0	26.3
Hypertension (Count of Participants)
Count of Participants [Participants]	11 24.4%	7 17.1%	18 20.9%
Dyslipidemia (Count of Participants)
Count of Participants [Participants]	7 15.6%	25 61%	32 37.2%
CD4+ T cell count (cells/mm3) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cells/mm3]	587	636	612

Outcome Measures

1. Primary Outcome

Title	Reactive Hyperemia Index (RHI) by Peripheral Arterial Tonometry (PAT)
Description	Ratio of the average pulse wave amplitude (PWA) over a 1 minute interval starting 1 minute following cuff release to the pre-occlusion PWA (average over 3.5 minutes pre-cuff inflation)
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)
Arm/Group Description	HIV+, HCV viremic at study entry	HIV+, HCV negative at study entry
Measure Participants	45	41
Median (Inter-Quartile Range) [ratio]	1.98	2.15

2. Secondary Outcome

Title	Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163)
Description	Serum hsCRP
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

All participants with available data.

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)
Arm/Group Description	HIV+/HCV viremic	HIV+/HCV-
Measure Participants	35	41
Median (Inter-Quartile Range) [mg/L]	0.6	1.3

3. Secondary Outcome

Title	Reactive Hyperemia Index (RHI)
Description	Ratio of the average pulse wave amplitude (PWA) over a 1 minute interval starting 1 minute following cuff release to the pre-occlusion PWA (average over 3.5 minutes pre-cuff inflation)
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)
Arm/Group Description	HIV+/HCV+, HCV treated	HIV+/HCV- at study entry
Measure Participants	31	29
Median (Inter-Quartile Range) [ratio]	1.88	2.09

4. Secondary Outcome

Title	Soluble Biomarkers (Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163)
Description	Serum hsCRP
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All participants with available data.

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)
Arm/Group Description	HIV+/HCV+, HCV treated	HIV+/HCV- at study entry
Measure Participants	30	16
Median (Inter-Quartile Range) [mg/L]	1.05	1.0

5. Secondary Outcome

Title	Insulin Resistance by HOMA-IR
Description	fasting insulin (μU/mL) x fasting glucose (mg/dl) / 405
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

All participants with available data.

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)
Arm/Group Description	HIV+/HCV+, HCV treated	HIV+/HCV- at study entry
Measure Participants	35	41
Median (Inter-Quartile Range) [HOMA-IR score]	3.86	2.24

6. Secondary Outcome

Title	Insulin Resistance by HOMA-IR
Description	fasting insulin (μU/mL) x fasting glucose (mg/dl) / 405
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All participants with available data

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)
Arm/Group Description	HIV+/HCV+, HCV treated	HIV+/HCV- at study entry
Measure Participants	30	16
Median (Inter-Quartile Range) [HOMA-IR score]	2.77	2.13

7. Secondary Outcome

Title	Framingham Risk Score (FRS), 10-year Risk (%)
Description	Estimate of 10-year risk for developing coronary heart disease (CHD), calculated as described in ATP III Executive Summary, JAMA, May 16, 2001-Vol 285, No. 19. Range of values is <1 to >/= 30% Higher risk % is worse predicted outcome.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

All participants with available data

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)
Arm/Group Description	HIV+/HCV viremic	HIV+/HCV-
Measure Participants	45	41
Median (Inter-Quartile Range) [percent, 10-year risk]	6.0	6.0

8. Secondary Outcome

Title	Framingham Risk Score (FRS), 10-year Risk (%)
Description	Estimate of 10-year risk for developing coronary heart disease (CHD), calculated as described in ATP III Executive Summary, JAMA, May 16, 2001-Vol 285, No. 19. Range of values is <1 to >/= 30% Higher risk % is worse predicted outcome.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

All participants with available data

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)
Arm/Group Description	HIV+/HCV+, HCV treated	HIV+/HCV- at study entry
Measure Participants	30	16
Median (Inter-Quartile Range) [percent, 10-year risk]	6.0	5.0

9. Secondary Outcome

Title	Change in RHI
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

All with available data

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)
Arm/Group Description	HIV+/HCV+, HCV treated	HIV+/HCV- at study entry
Measure Participants	31	29
Median (Inter-Quartile Range) [ratio]	-0.16	-0.03

10. Secondary Outcome

Title	Change in Level of Each Soluble Biomarker (Components of Fasting Lipid Panel, hsCRP, IL-6, D-dimer, sICAM-1, sE-selectin, Lp-PLA2, sCD14, sCD163)
Description	Change in serum hsCRP level
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

All participants with available data

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)
Arm/Group Description	HIV+/HCV viremic, HCV treated	HIV+/HCV-
Measure Participants	27	16
Median (Inter-Quartile Range) [mg/L]	0.40	0.00

11. Secondary Outcome

Title	Change in HOMA-IR
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

All participants with available data

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)
Arm/Group Description	HIV+/HCV+, HCV treated	HIV+/HCV- at study entry
Measure Participants	27	16
Median (Inter-Quartile Range) [HOMA-IR score]	0.34	0.28

12. Secondary Outcome

Title	Change in Framingham Risk Score (10-year Risk, %)
Description	Change in estimated 10-year risk (% risk) for developing coronary heart disease (CHD). Positive value indicates increase in estimated 10-year risk for CHD from baseline to Week 52. Negative value indicates decrease in estimated 10-year risk for CHD from baseline to Week 52.
Time Frame	Baseline to Week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A (HIV/HCV Coinfected)	Group B (HIV Monoinfected)
Arm/Group Description	HIV+/HCV viremic, HCV treated	HIV+/HCV-
Measure Participants	27	16
Median (Inter-Quartile Range) [percent]	1.0	0

Adverse Events

Time Frame	All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were not monitored/assessed.
Adverse Event Reporting Description	All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were not monitored/assessed.
Arm/Group Title	Group A (HIV/HCV Coinfected)		Group B (HIV Monoinfected)
Arm/Group Description	HIV+, HCV viremic at study entry		HIV+, HCV negative at study entry
All Cause Mortality
	Group A (HIV/HCV Coinfected)		Group B (HIV Monoinfected)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Group A (HIV/HCV Coinfected)		Group B (HIV Monoinfected)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Group A (HIV/HCV Coinfected)		Group B (HIV Monoinfected)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.