HIVPhase 4NCT03088410
Study of HIV-Infected and Uninfected Pregnant Woman/Child Dyads in Gaborone, Botswana
A Phase 4 study testing Zidovudine and Nevirapine in people with HIV and Insulin Sensitivity, run by Ann & Robert H Lurie Children's Hospital of Chicago at 1 site in Botswana.
Trial summary
The purpose of this study is to assess the early longitudinal metabolic effects including insulin sensitivity in HIV-exposed uninfected (HEU) children compared to HIV-unexposed uninfected (HUU) children; as well as to determine differences in the effects of neonatal zidovudine (AZT) vs. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV, Insulin Sensitivity, Diabetes Mellitus
- What is being tested?
- Zidovudine and Nevirapine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 495 participants
- Where
- 1 siteBotswana
- Study dates
- 22 Aug 2016to 31 Mar 2022
- Phase
- Phase 4
- 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 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- HIV-infected and uninfected pregnant women between 16-36 weeks GA are eligible for study enrollment.
- Women must be 18 years of older and able to provide informed consent for themselves and their infant to participate in the study.
- Participants must be Botswana citizens.
- Women must have evidence of HIV infection status. Women NOT documented as HIV seropositive must have documentation of HIV seronegativity during the present pregnancy at or after 32 weeks GA. Women who have an initial negative HIV test during the present pregnancy which was done at <32 weeks GA will need to undergo repeat testing on or after 32 weeks GA in accordance with national guidelines.
- HIV-uninfected women must be willing to undergo HIV pre-test counseling, rapid HIV testing and post-test counseling, referred to as HIV Testing and Counseling (HTC) during pregnancy.
- Women must be willing to remain in study area with their infant and attend scheduled study visits as described above until the child's 3rd birthday.
- For HIV-infected women, they must be on TDF/3TC or FTC/EFV or TDF/3TC or FTC/Dolutegravir at time of study enrollment or willing to initiate this treatment and continue throughout the period of breastfeeding, if not for their lifetime.
- At enrollment, all women must be willing to breastfeed exclusively for the first six months of life.
Who cannot join
- •Pre-existing maternal diabetes mellitus.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Tshilo Dikotla Study: Metabolic Outcomes of Children HIV/ARV-Exposed Uninfected in Botswana (MOCHA)
The purpose of this study is to assess the early longitudinal metabolic effects including insulin sensitivity in HIV-exposed uninfected (HEU) children compared to HIV-unexposed uninfected (HUU) children; as well as to determine differences in the effects of neonatal zidovudine (AZT) vs. nevirapine (NVP) prophylaxis on early longitudinal changes in insulin sensitivity in the first 3 years of life.
Read the detailed description
This study will consist of a nested randomized component of HIV-infected (HIV+) and -uninfected (HIV-) pregnant woman/child dyads in Botswana which will take place in Gaborone, Botswana at Botswana-Harvard AIDS Institute Partnership's (BHPs) clinical research facilities. A total of 300 HIV+ pregnant woman/fetus dyads on cART and 150 HIV- pregnant woman/fetus dyads will be evaluated for insulin sensitivity and followed through the child's 3rd birthday. Amongst HEU infants, participants will be randomized at birth 1:1 with 150 to receive neonatal AZT prophylaxis and 150 to receive neonatal NVP prophylaxis. Targeted metabolomics will be used to assess the role intermediary metabolites in insulin resistance and directly assess mitochondrial function using Seahorse XF96e technology. At the time of study enrollment, all women must be willing to exclusively breastfeed for the infant's first 6 months of life. If in utero and neonatal HIV/ARV exposures are found to be associated with derangements in intermediary metabolism such that HEU infants are at increased risk for insulin resistance by 3 years of age, this would impact screening and prevention strategies for diabetes in this vulnerable population and argue for further research to identify prenatal and neonatal ARV regimens with superior PMTCT efficacy but minimal adverse metabolic consequences.
- Conditions
- HIV, Insulin Sensitivity, Diabetes Mellitus
- Being tested
- Zidovudine, Nevirapine
- Medical subject headings
- Insulin Resistance, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZidovudineDrug
Also called AZT
neonatal 4 weeks prophylactic
NevirapineDrug
Also called NVP
neonatal 4 weeks prophylactic
| Study group | Role | What they receive |
|---|---|---|
| Nevirapine | Experimental | 150 HIV-Exposed Uninfected (HEU) infants on Nevirapine (NVP) Prophylaxis Receives: Drug: Nevirapine |
| Zidovudine | Active comparator | 150 HIV-Exposed Uninfected (HEU) infants on Zidovudine (AZT) Prophylaxis Receives: Drug: Zidovudine |
| HIV- unexposed Uninfected (HUU) Infants | No intervention | 150 HIV- unexposed Uninfected (HUU) Infants |
What is being measured
The primary outcome is the main question the study is designed to answer.
Homeo-static Model Assessment-Insulin Resistance (HOMA-IR)
[glucose (mg/dL) X insulin ( μU/mL)405]
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2017
- Study start22 Aug 2016
- Primary completion31 Mar 2022
- Study completion31 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 495 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ann & Robert H Lurie Children's Hospital of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jennifer Jao, Ann & Robert H Lurie Children's Hospital of Chicago
- Investigators
- Jennifer Jao, MD, MPH, Principal investigator, Ann & Robert H Lurie Children's Hospital of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03088410
- Sponsor's protocol ID
- IRB 2019-2922
- Other IDs
- R01DK109881, HRDC 00781
- Status last verified
- Jul 2022
- First submitted
- 3 Mar 2017
- Last updated
- 20 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Banda FM, Powis KM, Sun S, Makhema J, Masasa G, Yee LM, Jao J. Fetal biometry following in-utero exposure to dolutegravir-based or efavirenz-based antiretroviral therapy. AIDS. 2020 Dec 1;34(15):2336-2337. doi: 10.1097/QAD.0000000000002674. No abstract available.
PubMed 32910067Jao J, Sun S, Bonner LB, Legbedze J, Mmasa KN, Makhema J, Mmalane M, Kgole S, Masasa G, Moyo S, Gerschenson M, Mohammed T, Abrams EJ, Kurland IJ, Geffner ME, Powis KM. Lower Insulin Sensitivity in Newborns With In Utero HIV and Antiretroviral Exposure Who Are Uninfected in Botswana. J Infect Dis. 2022 Nov 28;226(11):2002-2009. doi: 10.1093/infdis/jiac416.
PubMed 36240387
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Tshilo Dikotla Study: Metabolic Outcomes of Children HIV/ARV-Exposed Uninfected in Botswana (MOCHA)
- ClinicalTrials.gov ID
- NCT03088410
- Acronym / sponsor ID
- IRB 2019-2922
- Conditions
- HIV, Insulin Sensitivity, Diabetes Mellitus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 495 participants (actual)
- Lead sponsor
- Ann & Robert H Lurie Children's Hospital of ChicagoUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 22 Aug 2016 (actual)
- Primary completion
- 31 Mar 2022 (actual)
- Study completion
- 31 Mar 2022 (actual)
- First posted
- 23 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the early longitudinal metabolic effects including insulin sensitivity in HIV-exposed uninfected (HEU) children compared to HIV-unexposed uninfected (HUU) children; as well as to determine differences in the effects of neonatal zidovudine (AZT) vs. nevirapine (NVP) prophylaxis on early longitudinal changes in insulin sensitivity in the first 3 years of life.
Detailed description
This study will consist of a nested randomized component of HIV-infected (HIV+) and -uninfected (HIV-) pregnant woman/child dyads in Botswana which will take place in Gaborone, Botswana at Botswana-Harvard AIDS Institute Partnership's (BHPs) clinical research facilities. A total of 300 HIV+ pregnant woman/fetus dyads on cART and 150 HIV- pregnant woman/fetus dyads will be evaluated for insulin sensitivity and followed through the child's 3rd birthday. Amongst HEU infants, participants will be randomized at birth 1:1 with 150 to receive neonatal AZT prophylaxis and 150 to receive neonatal NVP prophylaxis. Targeted metabolomics will be used to assess the role intermediary metabolites in insulin resistance and directly assess mitochondrial function using Seahorse XF96e technology. At the time of study enrollment, all women must be willing to exclusively breastfeed for the infant's first 6 months of life. If in utero and neonatal HIV/ARV exposures are found to be associated with derangements in intermediary metabolism such that HEU infants are at increased risk for insulin resistance by 3 years of age, this would impact screening and prevention strategies for diabetes in this vulnerable population and argue for further research to identify prenatal and neonatal ARV regimens with superior PMTCT efficacy but minimal adverse metabolic consequences.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Nevirapine | Experimental | Drug: Nevirapine150 HIV-Exposed Uninfected (HEU) infants on Nevirapine (NVP) Prophylaxis |
| Zidovudine | Active comparator | Drug: Zidovudine150 HIV-Exposed Uninfected (HEU) infants on Zidovudine (AZT) Prophylaxis |
| HIV- unexposed Uninfected (HUU) Infants | No intervention | –150 HIV- unexposed Uninfected (HUU) Infants |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- HIV-infected and uninfected pregnant women between 16-36 weeks GA are eligible for study enrollment.
- Women must be 18 years of older and able to provide informed consent for themselves and their infant to participate in the study.
- Participants must be Botswana citizens.
- Women must have evidence of HIV infection status. Women NOT documented as HIV seropositive must have documentation of HIV seronegativity during the present pregnancy at or after 32 weeks GA. Women who have an initial negative HIV test during the present pregnancy which was done at <32 weeks GA will need to undergo repeat testing on or after 32 weeks GA in accordance with national guidelines.
- HIV-uninfected women must be willing to undergo HIV pre-test counseling, rapid HIV testing and post-test counseling, referred to as HIV Testing and Counseling (HTC) during pregnancy.
Key exclusion criteria (1 listed)
- •Pre-existing maternal diabetes mellitus.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZidovudineAlso: AZTneonatal 4 weeks prophylactic | Drug | Zidovudine |
| NevirapineAlso: NVPneonatal 4 weeks prophylactic | Drug | Nevirapine |
Primary outcome
Homeo-static Model Assessment-Insulin Resistance (HOMA-IR)
Time frame: up to 3 years
[glucose (mg/dL) X insulin ( μU/mL)405]
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2022.
- Background: PubMed 32910067Banda FM, Powis KM, Sun S, Makhema J, Masasa G, Yee LM, Jao J. Fetal biometry following in-utero exposure to dolutegravir-based or efavirenz-based antiretroviral therapy. AIDS. 2020 Dec 1;34(15):2336-2337. doi: 10.1097/QAD.0000000000002674. No abstract available.
- Derived from this study: PubMed 36240387Jao J, Sun S, Bonner LB, Legbedze J, Mmasa KN, Makhema J, Mmalane M, Kgole S, Masasa G, Moyo S, Gerschenson M, Mohammed T, Abrams EJ, Kurland IJ, Geffner ME, Powis KM. Lower Insulin Sensitivity in Newborns With In Utero HIV and Antiretroviral Exposure Who Are Uninfected in Botswana. J Infect Dis. 2022 Nov 28;226(11):2002-2009. doi: 10.1093/infdis/jiac416.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Jao, MD, MPH principal investigator
Ann & Robert H Lurie Children's Hospital of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Zidovudine and Nevirapine in people with HIV and Insulin Sensitivity, run by Ann & Robert H Lurie Children's Hospital of Chicago at 1 site in Botswana.
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 8 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: finished, as of the sponsor's last update on 20 Jul 2022. 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 Botswana. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Homeo-static Model Assessment-Insulin Resistance (HOMA-IR) (time frame: up to 3 years). 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 NCT03088410, which also lists 2 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 20 Jul 2022.