Clinical trial NCT01107834: Heart Function in HIV-Negative Children Exposed to HIV and HAART
Official title: Left Ventricular Function in HIV-Negative Children Exposed to HIV and HAART In Utero
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: HIV
heart function
HAART
in utero
children
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2010-04-21
Enrollment: 60
Sex: ALL
Minimum age (years): 5
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV-negative children will be recruited through their HIV+ mothers who are seen at the AIDS Clinical Trials Unit at Washington University and surrounding St. Louis community clinics. HIV-negative children will be recruit through Washington University and surrounding St. Louis pediatric clinics, and through Washington University Volunteers for Health service.

Brief summary: HIV-uninfected children born to HIV+ women have low level heart problems at birth which may predispose them to heart failure, arrythmias and heart attack later in life. The impact of these heart problems on future heart health is unclear as it is unknown if heart problems in these children persist, worsen or resolve in pre-pubescence. The objective of this study is to characterize heart function in HIV-negative pre-pubertal children born to HIV+ women and exposed to HIV and HAART in utero and compare them to age and gender matched healthy children born to HIV-negative women. Through this objective we will determine if heart problems in HIV-negative children born to HIV+ women and exposed to HAART in utero persists, worsens, or resolves during pre-pubescence.

Detailed description: Significance:

Approximately 700,000 children annually are born to HIV-infected mothers throughout the world, but with the advent of perinatal highly active antiretroviral therapy (HAART), the majority of children are born uninfected in Westernized nations and those uninfected are increasing in developing nations. Uninfected children exposed to HIV and HAART in utero, have subclinical left ventricular dysfunction (LVD) at birth which may predispose them to heart failure, conduction abnormalities and myocardial infarction later in life. The impact of this LVD on future cardiac risk is unclear as it is unknown if LVD in these children persist, worsen or resolve in pre-pubescence.

Study objectives:

The objective of this study is to characterize left ventricular function in HIV-negative pre-pubertal children born to HIV+ women and exposed to HIV and HAART in utero and compare them to age and gender matched healthy children born to HIV-negative women. Through this objective we will determine if LVD in HIV-negative children born to HIV+ women and exposed to HAART in utero persists, worsens, or resolves during pre-pubescence. If LVD persists or worsens in pre-pubescence, these data will lead to future studies examining mechanisms of and treatments for LVD in these children and will significantly impact the clinical monitoring and care of these children. If LVD resolves during pre-pubescence, then these data will provide important information that clinical cardiac monitoring may not be critical in this population.

Methods:

We plan to examine left ventricular function in 30 HIV-negative children born to HIV+ women and exposed to HAART in utero and compare them to 30 healthy age and gender matched children born to HIV-negative women. Left ventricular function will be examined by 2-D, Doppler and Tissue Doppler imaging echocardiography using a General Electric Vivid 7® ultrasound machine. Left ventricular measures will include left ventricular structure and dimensions, systolic and diastolic flow rates, wall velocities during systole and diastole and systolic and diastolic strain and strain rates (sensitive measures of myocardial contractility). Echocardiographic measures will take place in the Cardiovascular Imaging Laboratory (CVIL) at Washington University School of Medicine by a certified cardiac ultrasonographer and data will be processed, analyzed and interpreted by the ultrasonographer, a consulting cardiologist and the principal investigator.

Outcomes:

Primary outcomes will include measures of left ventricular function: left ventricular mass, left ventricular end diastolic dimension, fractional shortening, systolic and diastolic wall velocities (tissue Doppler imaging) and systolic and diastolic strain and strain rates (2-D speckle tracking methodology).

Eligibility criteria: Inclusion Criteria:

1. Age 5-12 years
2. Tanner stage I-III
3. Born to HIV+ mother
4. No HIV infection
5. Had taken standard of care prophylactic HAART at birth-1 month of age
6. Child currently not taking medications or have medical diagnosis that would affect left ventricular function
7. Mother was taking HAART during pregnancy (standard of care)
8. Mother was not using illegal drugs during pregnancy
9. No intrauterine growth restriction diagnosis during pregnancy
10. During pregnancy, mother will not have a diagnosis of type 2 diabetes or gestational diabetes.

Exclusion Criteria:

1. Age 5-12 years
2. Tanner stage I-III
3. Born to HIV-negative mother
4. Mother was not a frequent exerciser during pregnancy (\>2x/week)
5. Mother will not have gestational diabetes or a diagnosis of type 2 diabetes during pregnancy of the child being studied
6. Child currently not taking medications or have medical diagnosis that would affect left ventricular function

Primary outcomes:
measure: Left Ventricular Mass Index
timeFrame: Baseline
measure: Fractional Shortening
timeFrame: Baseline
Secondary outcomes:
measure: Global Strain Rate
timeFrame: Baseline
measure: Systolic Myocardial Velocity During Systole (S')
timeFrame: Baseline
measure: Early to Late Diastolic Filling Ratio
timeFrame: Baseline
measure: Myocardial Wall Velocity During Early Diastole
timeFrame: Baseline
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: William T Cade, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cade WT, Waggoner AD, Hubert S, Krauss MJ, Singh GK, Overton ET. Reduced diastolic function and left ventricular mass in HIV-negative preadolescent children exposed to antiretroviral therapy in utero. AIDS. 2012 Oct 23;26(16):2053-8. doi: 10.1097/QAD.0b013e328358d4d7.