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In Utero Drug ExposureARTMOMSBABESNCT04763668

Cardiometabolic Health of Children Exposed to Anti-retroviral Therapy (ART) in Utero

An observational study of In Utero Drug Exposure, run by Walter Sisulu University at 1 site in South Africa.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The Human Immunodeficiency Virus (HIV) has been recently linked to increased risk for cardiovascular diseases (CVDs). The prevalence of cardiovascular diseases and its risk factor, hypertension, are very high in African communities especially in the working age group which also happens to have the bulk of young female… Read more about this study

Who is it for?
Any age, women onlyHealthy volunteers can take part
Conditions the study is for
In Utero Drug Exposure
What is being tested?
Pregnant HIV positive women on ARTs and Babies born to HIV positive mothers on ARTs
How many people
320 participants
Where
1 siteSouth Africa
Study dates
20 May 2021to 31 Dec 2023
How long will I take part?
3 Years
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • Women only
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Study population: Sub-Saharan pregnant women of African ancestry living in South Africa

Who may be able to join

  • Cases: sub-Saharan women with singleton uncomplicated 11-14 week old pregnancies, be HIV positive and have been on ARTs for at least four months before pregnancy.
  • Controls: 11-14 week old pregnant HIV negative women.

Who cannot join

  • Pregnant women with type 2 diabetes, gestational diabetes, renal and cardiovascular diseases or any critical health.

Trial locations and contacts

1 site in 1 country.

South Africa1 site
  • Umtata General Hospital

    Mthatha, Eastern Cape, 5099

Other trials in South Africa

About this study

Official title: Assessment of the Impact of HIV Infection an Anti-retroviral Therapy (ART) on the Cardiometabolic Health of Pregnant Mothers and Their Offspring

The Human Immunodeficiency Virus (HIV) has been recently linked to increased risk for cardiovascular diseases (CVDs). The prevalence of cardiovascular diseases and its risk factor, hypertension, are very high in African communities especially in the working age group which also happens to have the bulk of young female adults in the reproductive age. Hypertension in African children is becoming a real cause for concern though its etiology remains elusive. Thanks to antiretroviral therapy (ART) use, many more infected persons live long enough to reproduce, consequently, an increasing number of children are being born to mothers who are infected with HIV. Could it be that in utero exposure of these children to HIV/ART contribute in programming them for increased risk for cardiovascular diseases thus making them more vulnerable to hypertension in childhood and adulthood? This study is aimed at exploring the possible association of in utero exposure to the HIV/ART environment and an increased risk for cardiovascular disease.

Read the detailed description
  1. Sample size calculation The number of participants required to show statistical significance is based on previously published studies in which vascular function was assessed in HIV patients (Agu et al., 2019). An error probability (α) of 0.05, and power (1- β) of 0.80 and an average effect size (d) of 0.5 were used to calculate the sample size (n= 64 persons). Assuming a 25% drop out rate, we will use N = (64 + (64*25)/100) = 80 mothers/group to ensure that we will have enough sample size/group to show statistical significance. Total number of participating mothers will therefore be 160 (80 cases and 80 controls) and their offspring - 160.

II. Ethical approval Ethical consent and permission to carry out the research project will be obtained from the Faculty of Health Sciences Research and Ethics Committee (HRSEC) at Walter Sisulu University (WSU). The purpose of the study will be explained to women attending the antenatal clinic in the Umtata General and Nelson Mandela Academic Hospitals, Mthatha, Eastern Cape Province. Pregnant women who will be willing to participate will be required to sign informed consent forms to participate in the study and to allow their children to participate in the study from birth.

III. Study design A prospective case control study design will be used in this study.

IV. Selection criteria Sub-Saharan women with singleton uncomplicated 11-14 week old pregnancies, be HIV positive for the case group and HIV negative for the control group. Pregnant women with type 2 diabetes, gestational diabetes, renal and cardiovascular diseases or any critical health condition will be excluded from the study

  1. Experimental Plan

Work Package 1 (Pregnant women):

Three antenatal visits will be recorded for this study - These visits will be done during the first, second and third trimesters of gestation.

The following information and parameters will be assessed during each antenatal visit:

  1. Baseline information: Maternal demographic, obstetric and family history of cardiovascular diseases during the first visit using a questionnaire - once off at the start of the study.
  2. Anthropometric measurements: Height and weight will be determined as per recommendations of the NHANES, 2009 recommendations. BMI will be calculated using the formula weight/(height (m) x height (m)).
  3. Blood pressure measurements: Office blood pressure will be measured as described by Muntner et al., (2019) in triplicates at three minutes intervals after 10 minutes of rest in the seated position. This will be followed by 24 h ambulatory blood pressure measurement for determination of day time/night time blood pressure and dipping phenotype.
  4. Placental morphometry, architecture and vascularization: Uterine arteries, umbilical artery and middle cerebral artery and uterine artery mean pulsating index will be determined by ultrasound. Foetal cerebroplacental ratio will be calculated when possible.
  5. Endothelial function tests: Carotid intima media thickness, pulse wave velocity and flow mediated slowing and retinal artery assessment will be measured using ultrasonography and Vicorder (Ellins, 2017). Retinal microvasculature will be studied to determine endothelial function.
  6. Markers of endothelial function: Endocan, asymmetric dimethyl arginine (ADMA) and nitric oxide (NO) will be assayed using ELISA kits as per manufacturers' instructions.
  7. Markers of oxidative stress: Lipid peroxidation, total antioxidant capacity and 8-hydoxyl-2-deoxyguanine (8-OHdG) will be determined using ELISA kits as per manufacturer's protocols.
  8. Lipid profile indices: Total cholesterol, triglyceride, LDL cholesterol and HDL cholesterol, and oxidized LDL-cholesterol will be measured as per manufacturer's protocol.
  9. Insulin Resistance: Fasting glucose, glycated haemoglobin and insulin concentrations will be determined using kits as per manufacturer's methods. The HOMA-IR formula will be used to calculate insulin resistance from fast glucose and insulin.
  10. Renal function indices: glomerular filtration rate (GFR), creatinine and albumin will be determined and albumin to creatinine ratio computed.

Work Package 2 (Neonates):

During delivery, cord blood will be collected for assessment of markers of oxidative stress and endothelial function and epigenetic markers in the foetus. The following data will be collected:

  1. Anthropometric measurements: The weight, length, cranial circumference of the child will be measured.
  2. Blood pressure measurements: Casual blood pressure will be measured by oscillometry using disposable arm-size appropriate cuffs. Blood pressure will be measure in triplicates with five minutes intervals at least one hour after baby's meal and when baby is sleeping (Samantha et al, 2015).
  3. Markers of endothelial function: Endocan, asymmetric dimethyl arginine (ADMA) and nitric oxide (NO) will be assayed using ELISA kits as per manufacturers' instructions.
  4. Markers of oxidative stress: Lipid peroxidation, total antioxidant capacity and 8-hydoxyl-2-deoxyguanine (8-OHdG) will be determined using ELISA kits as per manufacturer's protocols.
  5. Lipid profile indices: Total cholesterol, triglyceride, LDL cholesterol and HDL cholesterol, and oxidized LDL-cholesterol will be measured as per manufacturers protocol.
  6. Insulin Resistance: cord blood glucose and insulin concentrations will be determined as per manufacturer's methods. The HOMA-IR formula will be used to calculate insulin resistance.
  7. Renal function indices: glomerular filtration rate (GFR), creatinine and albumin will be determined. The Albumin to creatinine ratio will also be determined.
  8. Epigenetic markers: Urine concentrations of 5-methyl-2-deoxycytidine and trimethyl histone H3K9 using Elisa kit as per manufacturer's methods.

Work Package 3 (Mothers at 3 months post-natal follow-up)

Mothers will followed up three months after delivery. During this visit no blood nor will urine samples be collected from the mothers. Urine samples will be collected from babies for measurement of CVD risk makers. The following data will be collected:

  1. Anthropometric measurements: Height and weight will be determined as per recommendations of the NHANES, 2009 recommendations. BMI will be calculated using the formula weight/(height (m) x height (m)) for both mother and baby.
  2. Blood pressure measurements: Office blood pressure will be measured as described by Puntner et al., (2019) in triplicates at three minutes intervals after 10 minutes of rest in the seated position. This will be followed by 24 h ambulatory blood pressure measurement for determination of day time/night time blood pressure and dipping phenotype - mother
  3. Blood pressure will be measured in the baby in the supine position.
  4. Endothelial function tests: Carotid intima media thickness, pulse wave velocity and flow mediated slowing and retinal artery assessment will be measured using ultrasonography and Vicorder (Ellins, 2017). Retinal microvasculature will be studied to determine endothelial function in the mother.
  5. Endothelial function tests: pulse wave velocity and flow mediated slowing using the Vicorder in the baby (Ng et al, 2018).

Work Package 4 (Child):

Data will be collected from children at three, twelve and twenty four months after birth as follows:

  1. Anthropometric measurements: The weight, length, cranial circumference of the child will be measured.
  2. Blood pressure measurements: Casual blood pressure will be measured by oscillometry using disposable arm-size appropriate cuffs. Blood pressure will be measure in triplicates with five minutes intervals at least one hour after baby's meal and when baby is sleeping (Samantha et al, 2015).
  3. Endothelial function tests: pulse wave velocity and flow mediated slowing using the Vicorder (Ng et al, 2018).
  4. Markers of endothelial function: Urine samples will be collected for Endocan, asymmetric dimethyl arginine (ADMA) and nitric oxide (NO) assays using ELISA kits as per manufacturers' instructions.
  5. Markers of oxidative stress: Lipid peroxidation, total antioxidant capacity and 8-hydoxyl-2-deoxyguanine (8-OHdG) will be determined in urine samples using ELISA kits as per manufacturer's protocols.
  6. Renal function indices: Urine creatinine and albumin will be determined. The Albumin to creatinine ratio will also be determined.
  7. Epigenetic markers: Urine concentrations of 5-methyl-2-deoxycytidine and trimethyl Histone H3K9 using elisa kit as per manufacturer's methods.
  8. Endothelial function tests: pulse wave velocity and flow mediated slowing using the Vicorder (Ng et al, 2018).
Being tested
Pregnant HIV positive women on ARTs, Babies born to HIV positive mothers on ARTs
Keywords
ART, neonate, HIV infection, risk, cardiovascular disease, pregnant
Medical subject headings
HIV Infections, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pregnant HIV positive women on ARTsOther

    Cardiovascular disease risk in pregnant HIV positive women on ARTs

  • Babies born to HIV positive mothers on ARTsOther

    cardiovascular disease risk in the offspring of HIV positive mothers on ARTs

Study groups in NCT04763668
Study groupRoleWhat they receive
Pregnant HIV positive women on ARTSub-Saharan women with singleton uncomplicated 11-14 week old pregnancies at recruitment, HIV positive and have been on ARTs for at least four months before pregnancy. Participants must not have type 2 diabetes, gestational diabetes, renal / cardiovascular diseases or any critical health condition.
Receives: Other: Pregnant HIV positive women on ARTs
Pregnant HIV negative womenSub-Saharan women with singleton uncomplicated 11-14 week old pregnancies at recruitment, HIV negative. Participants must not have type 2 diabetes, gestational diabetes, renal / cardiovascular diseases or any critical health condition.
Receives: Other: Pregnant HIV positive women on ARTs
Babies born to HIV positive mothers on ARTsAll babies born to pregnant HIV positive women on ARTs who were in the first arm of the study
Receives: Other: Babies born to HIV positive mothers on ARTs
Babies born to HIV negative mothersAll babies born to pregnant HIV negative women who were in the first arm of the study.
Receives: Other: Babies born to HIV positive mothers on ARTs

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Assessment of changes in cardiovascular risk profile during pregnancy in pregnant HIV positive women on ARTs

    Cardiovascular risk will be assessed in pregnant

    Measured: March 2021 to March 2022

  2. Assessment of of CVD risk in offspring of HIV positive mothers on ARTs

    Cardiovascular risk will be assessed in the offspring of HIV positive mothers on ART at three time point: at birth, three, twelve and twenty months after birth.

    Measured: March 2021 to March 2022

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Feb 2021
  2. Study start20 May 2021 (estimated)
  3. Primary completion31 Dec 2021 (estimated)
  4. Study completion31 Dec 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Prospective
Enrolment
320 participants (estimated)
Target duration
3 Years
IDs, dates and publications
ClinicalTrials.gov ID
NCT04763668
Sponsor's protocol ID
129245
Acronym
ARTMOMSBABES
Status last verified
May 2021
First submitted
16 Feb 2021
Last updated
6 May 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Collected data will be shared in the form of conference presentations and published peer-reviewed articles.

Publications

  • Agu CE, Uchendu IK, Nsonwu AC, Okwuosa CN, Achukwu PU. Prevalence and associated risk factors of peripheral artery disease in virologically suppressed HIV-infected individuals on antiretroviral therapy in Kwara state, Nigeria: a cross sectional study. BMC Public Health. 2019 Aug 20;19(1):1143. doi: 10.1186/s12889-019-7496-4.

    PubMed 31429736
  • Ellins EA, Smith KE, Lennon LT, Papacosta O, Wannamethee SG, Whincup PH, Halcox JP. Arterial pathophysiology and comparison of two devices for pulse wave velocity assessment in elderly men: the British regional heart study. Open Heart. 2017 Dec 17;4(2):e000645. doi: 10.1136/openhrt-2017-000645. eCollection 2017.

    PubMed 29344365
  • Muntner P, Shimbo D, Carey RM, Charleston JB, Gaillard T, Misra S, Myers MG, Ogedegbe G, Schwartz JE, Townsend RR, Urbina EM, Viera AJ, White WB, Wright JT Jr. Measurement of Blood Pressure in Humans: A Scientific Statement From the American Heart Association. Hypertension. 2019 May;73(5):e35-e66. doi: 10.1161/HYP.0000000000000087.

    PubMed 30827125
  • Ng KYB, Simpson NAB, Cade JE, Greenwood DC, Mcardle HJ, Ciantar E, Alwan NA. Is infant arterial stiffness associated with maternal blood pressure in pregnancy? Findings from a UK birth cohort (Baby VIP study). PLoS One. 2018 Jul 12;13(7):e0200159. doi: 10.1371/journal.pone.0200159. eCollection 2018.

    PubMed 30001353
  • Samanta M, Mondal R, Ray S, Sabui TK, Kundu CK, Hazra A, Chatterjee K, Sarkar D. Blood pressure variation with gestational age and birth weight in Indian newborn. J Trop Pediatr. 2015 Jun;61(3):197-205. doi: 10.1093/tropej/fmv019. Epub 2015 Mar 31.

    PubMed 25833095

Questions about this trial

What is this clinical trial studying?

An observational study of In Utero Drug Exposure, run by Walter Sisulu University at 1 site in South Africa.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 6 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assessment of changes in cardiovascular risk profile during pregnancy in pregnant HIV positive women on ARTs (time frame: March 2021 to March 2022). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04763668, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2021.

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