Ignite Creation Date:
2025-12-25 @ 2:46 AM
Ignite Modification Date:
2026-03-05 @ 10:45 AM
Study NCT ID:
NCT05923333
Status:
RECRUITING
Last Update Posted:
2024-08-22
First Post:
2023-06-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
B. Infantis Supplementation to Improve Immunity in Infants Exposed to HIV
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000163', 'term': 'Acquired Immunodeficiency Syndrome'}, {'id': 'D003141', 'term': 'Communicable Diseases'}], 'ancestors': [{'id': 'D015658', 'term': 'HIV Infections'}, {'id': 'D000086982', 'term': 'Blood-Borne Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D015229', 'term': 'Sexually Transmitted Diseases, Viral'}, {'id': 'D012749', 'term': 'Sexually Transmitted Diseases'}, {'id': 'D016180', 'term': 'Lentivirus Infections'}, {'id': 'D012192', 'term': 'Retroviridae Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D012897', 'term': 'Slow Virus Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007153', 'term': 'Immunologic Deficiency Syndromes'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 200}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-08-11', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-08', 'completionDateStruct': {'date': '2027-06', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-08-20', 'studyFirstSubmitDate': '2023-06-19', 'studyFirstSubmitQcDate': '2023-06-19', 'lastUpdatePostDateStruct': {'date': '2024-08-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-06-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-06', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Presence of total B. infantis and B. infantis Rosell®-33 in stool', 'timeFrame': '4 - 36 weeks of age', 'description': 'qPCR will be used to assess whether B. infantis Rosell®-33 colonized.'}, {'measure': 'Infant neurodevelopment milestones', 'timeFrame': '24 and 36 weeks of age', 'description': 'Comprehensive neurodevelopment assessment will be conducted, e.g. using the Bayley Scales of Infant and Toddler Development, 3rd edition, or similar assessment tools, and developmental scores compared between the two arms, as well as the proportion of infants passing each developmental area assessed. Higher scores indicate better outcomes.'}, {'measure': 'Infant growth', 'timeFrame': '4 - 36 weeks of age', 'description': 'Infant anthropometry will be recorded at each visit to calculate infant length for age (LAZ), weight for age (WAZ) and weight for length (WLZ) Z scores and will be compared between the two arms.'}, {'measure': 'All-cause infectious morbidity', 'timeFrame': '4 - 36 weeks of age', 'description': 'Infectious morbidity data will be quantify and compare occurrence of infectious morbidity outcomes between randomisation arms.'}, {'measure': 'Vaccine antibody titres', 'timeFrame': '4 - 36 weeks of age', 'description': 'Antibody titres to early childhood vaccines will be assessed and compared by treatment arm.'}], 'primaryOutcomes': [{'measure': 'Gut microbiome', 'timeFrame': '4 weeks of age', 'description': 'Alpha (Shannon) and Beta (Bray Curtis and UniFrac) diversity metrics on the entire microbial communities, assessed by bacterial shotgun metagenomics of infant stool, will be compared between treatment arms'}, {'measure': 'Markers of intestinal inflammation and microbial translocation', 'timeFrame': '4 - 36 weeks of age', 'description': 'Concentration of markers of intestinal inflammation and microbial translocation (Lipocalin-2 (Lcn-2), sCD163, I-FABP and LBP measured by ELISA in infant plasma) will be compared cross-sectionally at each time point between groups using Mann-Whitney U tests'}, {'measure': 'BCG vaccine respone', 'timeFrame': '7 weeks of age', 'description': 'Frequencies of total net cytokine producing cells in response to stimulation with BCG will be compared between arms.'}, {'measure': 'BCG vaccine respone', 'timeFrame': '36 weeks of age', 'description': 'Frequencies of total net cytokine producing cells in response to stimulation with BCG will be compared between arms.'}], 'secondaryOutcomes': [{'measure': 'Longitudinal succession in gut microbiota composition, diversity and function', 'timeFrame': '4 - 36 weeks of age', 'description': 'Longitudinal multi-omic variation will be visualized using PCoA and tSNE plots, and cross-sectional differences in multi-omic profiles will be assessed using PERMANOVAs.'}, {'measure': 'Stool metabolome', 'timeFrame': '4 weeks of age', 'description': 'For cross-sectional metabolite differential abundance analyses, we will use generalized linear regression (continuous dependent variable) and logistic regression (Boolean dependent variable) with an FDR correction.'}, {'measure': 'T cell subsets frequencies', 'timeFrame': '4 - 36 weeks of age', 'description': 'T cell subsets frequencies will be compared cross-sectionally between groups'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Hiv', 'Vaccine Reaction', 'Microbial Colonization', 'Infant Development']}, 'referencesModule': {'references': [{'pmid': '37853370', 'type': 'DERIVED', 'citation': 'Happel AU, Rametse L, Perumaul B, Diener C, Gibbons SM, Nyangahu DD, Donald KA, Gray C, Jaspan HB. Bifidobacterium infantis supplementation versus placebo in early life to improve immunity in infants exposed to HIV: a protocol for a randomized trial. BMC Complement Med Ther. 2023 Oct 18;23(1):367. doi: 10.1186/s12906-023-04208-0.'}]}, 'descriptionModule': {'briefSummary': 'The primary objectives of this study are to evaluate the effect of early-life B. infantis Rosell®-33 supplementation in infants exposed to HIV on:\n\n* gut microbiome composition and diversity at 4 weeks of life\n* markers of intestinal inflammation and microbial translocation at 4 weeks of life\n* Th1 cytokine responses to BCG at 7 weeks and 36 weeks of life\n\nThe secondary objectives include to evaluate the effect of B. infantis Rosell®-33 supplementation on:\n\n* longitudinal succession of the gut microbiota composition, diversity and function\n* relative and absolute abundance of B. infantis in infant stool during the first 36 weeks of life\n* stool metabolome\n* T cell subset ontogeny during the first 9 months of life.\n\nExploratory objectives are to evaluate whether B. infantis Rosell®-33 supplementation improves:\n\n* infant growth\n* all-cause morbidity\n* neurodevelopment during the first 9 months of life\n* antibody responses to early childhood vaccines', 'detailedDescription': 'Infants who are born to mothers with HIV (exposed but uninfected; iHEU) are at higher risk of morbidity and display multiple immune alterations compared to infants who are HIV-unexposed (iHU). Easily implementable strategies to improve immunity of iHEU, and possibly subsequent health outcomes, are needed. iHEU have altered gut microbiome composition and bifidobacterial depletion, and relative abundance of Bifidobacterium infantis has been associated with immune ontogeny, including humoral and cellular vaccine responses. Therefore, a randomized trial of B. infantis Rosell®-33 versus placebo given during the first month of life in South African iHEU will be conducted.\n\nThis is a parallel, randomised, controlled study. Two-hundred breastfed iHEU will be enrolled from the Khayelitsha Site B Midwife Obstetric Unit in Cape Town, South Africa and 1:1 randomised to receive 8 x109 CFU B. infantis Rosell®-33 daily or placebo for the first 4 weeks of life, starting on day 1-3 of life. Infants will be followed over 36 weeks with extensive collection of meta-data and samples.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '50 Years', 'minimumAge': '0 Days', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria Mother:\n\n* Willing and able to provide signed and dated informed consent form\n* 18 years of age or older\n* Documented HIV seropositive\n* Antiretroviral therapy initiated before the third trimester of pregnancy\n* Planning on exclusively breastfeeding the infant for the first 6 months of life\n\nInclusion Criteria Infant:\n\n* Documented HIV seronegative at birth\n* Born at term (completed at least 37 weeks of gestation)\n* Birth weight \\>2.4kgs\n\nExclusion Criteria:\n\n* Severe illnesses, e.g. Sepsis\n* current TB or known household TB contact\n* Chronic disorder or medications (other than antiretrovirals and cotrimoxazole prophylaxis) that in the opinion of the investigator would alter immunity\n* Pregnancy or delivery complications including birth asphyxia, seizures, sepsis, major congenital anomalies or congenital infections\n* Known contraindications to components of the interventional products\n* Taking additional probiotics or prebiotics\n* Any condition that in the opinion of the investigator would make participation in the trial unsafe'}, 'identificationModule': {'nctId': 'NCT05923333', 'acronym': 'BifIID', 'briefTitle': 'B. Infantis Supplementation to Improve Immunity in Infants Exposed to HIV', 'organization': {'class': 'OTHER', 'fullName': 'University of Cape Town'}, 'officialTitle': 'Bifidobacterium Infantis Supplementation in Early Life to Improve Immunity in Infants Exposed to HIV: a Randomized, Placebo-controlled, Double-blind Trial', 'orgStudyIdInfo': {'id': '697/2022'}, 'secondaryIdInfos': [{'id': 'R01HD109089', 'link': 'https://reporter.nih.gov/quickSearch/R01HD109089', 'type': 'NIH'}, {'id': 'PACTR202301748714019', 'type': 'REGISTRY', 'domain': 'Pan African Clinical Trials Registry'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'B. infantis Rosell®-33', 'description': 'Participants will receive 8 x 109 CFU B. infantis Rosell®-33 per dose (single microbial active ingredient) and carrier material (maltodextrin) for 28 days from day 1-3 of life.', 'interventionNames': ['Dietary Supplement: B. infantis Rosell®-33']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Participants will receive placebo (containing all materials besides B. infantis Rosell®-33) for 28 days from day 1-3 of life.', 'interventionNames': ['Dietary Supplement: Placebo']}], 'interventions': [{'name': 'B. infantis Rosell®-33', 'type': 'DIETARY_SUPPLEMENT', 'description': 'B. infantis Rosell®-33 + maltodextrin', 'armGroupLabels': ['B. infantis Rosell®-33']}, {'name': 'Placebo', 'type': 'DIETARY_SUPPLEMENT', 'description': 'Maltodextrin', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Cape Town', 'status': 'RECRUITING', 'country': 'South Africa', 'contacts': [{'name': 'Busi Tyhenge', 'role': 'CONTACT'}], 'facility': 'Khayelitsha Site B Midwife Obstetric Unit', 'geoPoint': {'lat': -33.92584, 'lon': 18.42322}}], 'centralContacts': [{'name': 'Heather Jaspan, MD PHD', 'role': 'CONTACT', 'email': 'hbjaspan@gmail.com', 'phone': '2068543336'}, {'name': 'Anna-Ursula Happel, PhD', 'role': 'CONTACT', 'email': 'anna.happel@uct.ac.za', 'phone': '+ 27 21 406 6823'}], 'overallOfficials': [{'name': 'Heather Jaspan, MD PHD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Seattle Children's Hospital"}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Cape Town', 'class': 'OTHER'}, 'collaborators': [{'name': "Seattle Children's Hospital", 'class': 'OTHER'}, {'name': 'University of Stellenbosch', 'class': 'OTHER'}, {'name': 'Institute for Systems Biology', 'class': 'OTHER'}, {'name': 'Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)', 'class': 'NIH'}, {'name': 'University of Washington', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Anna-Ursula Happel', 'investigatorAffiliation': 'University of Cape Town'}}}}