The Pediatric HIV Nutrition Study in Uganda (NOURISH)

The Role of Nutrition as a Determinant of Immune Function and Pharmacological Outcome Amongst HIV Infected Malnourished Children in Uganda

This will be cohort study design with both qualitative and quantitative methods of data collection. The investigators are aiming to study 64 HIV positive children as healthy controls either initiating ART or already on ART and 86 malnourished HIV infected children on ART or naïve initiating ART and RUTF aged between 6 months to 12 years. Primary carers will be asked to provide informed consent whereby the children and primary carers will be enrolled into the study and followed up for 12 weeks.

Study Overview

• Status: Unknown
• Conditions: Child Nutrition Disorders
• Intervention / Treatment: Dietary supplement: RUTF

Detailed Description

BACKGROUND: Malnutrition and Human Immunodeficiency Virus (HIV) infection are intimately linked and present a serious health challenge in Africa. Approximately 30-50% of children in Uganda with severe acute malnutrition (SAM) are HIV infected. Studies on nutrition as a determinant of immune response and drug metabolism in malnourished children are unknown.

GAP: Clinicians have noted that certain patients deteriorate after starting ART and nutritional supplementation despite viralogical suppression and immunological improvement with a paradoxical emergence of certain opportunistic infections, electrolyte derangement and malnutrition hence IRIS or re-feeding syndrome (RF). There is paucity of data on nutrition as a determinant of immune and pharmacological response amongst HIV infected malnourished children despite malnutrition being common.

HYPOTHESIS: Well-nourished HIV infected children ART naïve or experienced will have a better nutritional, clinical, immunological and pharmacological outcome than malnourished children ART naïve or experienced.

METHODS: A cohort design studying 75 malnourished HIV infected children on ART and RUTF comparing them to 75 well-nourished children ART naive or experienced aged between 6 months to 12 years after primary carers have provided informed consent will be enrolled into the study and followed up for 12 weeks.

IMPACT: This study will endeavor to provide appropriate information that will enhance the management of malnourished HIV infected children in the context of both ART and RUTF and their impact on immune response and drug metabolism. The study will also generate other research questions that need to be addressed in order to optimize HIV services amongst malnourished children.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Uganda
  • Kampala, Uganda, 256
    • Recruiting
    • Infectious Diseases Institute
    • Contact: Mohammed Lamorde, PhD; Phone Number: 320 +256312307000; Email: mlamorde@idi.co.ug
    • Principal Investigator: Andrew Kambugu, MMED
  • Kampala, Uganda, 256
    • Recruiting
    • Mildmay International Centre Kampala
    • Contact: Judy Orikiiriza, MMED; Phone Number: 244 +256307000; Email: jorikiiza@idi.co.ug
    • Contact: Jane Nakaweesi, MMED; Phone Number: +256 312 210 200; Email: nakawesijane@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV-infected children aged 6 months to 12 years, including Well Nourished (WN), Moderately Acute Malnutrition (MAM) and Severe Acute Malnutrition (SAM) patients initiating on ART within 2 weeks, whose carer is aged ≥18 years and has provided informed consent.
• Malnourished HIV-infected children aged 6 months to 12 years stabilized on ART for at least 6 months and initiating on RUTF, whose carer is aged ≥18 years and has provided informed consent.

Exclusion Criteria:

1. Previous enrollment in a nutritional therapeutic program in the last 3 months
2. Children involved in an on-going nutrition study
3. Children who have previously received the tuberculin skin test (TST) or mantoux or purified protein derivative (PPD) in the last 3 months.
4. Children with clinically suspected or confirmed malignancy
5. Children exhibiting any specific food intolerance
6. Children who are vomiting profusely (over 3 times daily)
7. Children living outside 50 km radius from Infectious Diseases Institute at Mulago, Kampala
8. Children whose carers do not want to disclose their home address.
9. Children whose cause of malnutrition is compounded by congenital malformations, chromosomal disorders, metabolic disorders, congenital immune disorders, cerebral palsy
10. Children with a severe disability limiting the possibility of investigations
11. Children who plan to leave the catchment area in the next 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Well-nourished HIV+ ART naive; These children aged between 6months-12years will be followed up for 12weeks to look at their nutrition, immune and pharmacological responses. They will receive routine nutritional and ART adherence counseling
Active Comparator: Moderately-malnourished HIV+; RUTF; These children aged between 6months - 12years, ART naive or experienced, will be initiating ready-to-use-therapeutic(RUTF) food and will be followed up for 12 weeks to see the effect of nutrition supplementation on immune and pharmacological responses	Dietary supplement: RUTF; This is ready-to-use-therapeutic-food; Other Names: Ready-to-Use-Therapeutic-Food
Active Comparator: Severely acute-malnourished HIV+; RUTF; These children aged between 6months - 12years, ART naive or experienced, will be initiating ready-to-use-therapeutic(RUTF) food and will be followed up for 12 weeks to see the effect of nutrition supplementation on immune and pharmacological responses	Dietary supplement: RUTF; This is ready-to-use-therapeutic-food; Other Names: Ready-to-Use-Therapeutic-Food

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in numbers of circulating immune cell population and their capacity to release cytokines	Immune response	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Immune reconstitution inflammatory syndrome (IRIS)	Episodes of Opportunistic infections - Clinical outcomes	12 weeks
Occurrence of re-feeding syndrome	Episodes of Opportunistic infections - Clinical outcomes	12 weeks
Pharmacological: Cmax	Cmax of Non-nucleotide reverse - transcriptase inhibitors (NNRTI) and Protease Inhibitors(PIs) at 0weeks, 6weeks,12weeks	12 weeks
Pharmacological: AUC	Area Under Curve (AUC) Time Frame: 0weeks, 6weeks, 12weeks for nevirapine and lopinvir/retonavir	12 weeks
Number of participants with adverse events	Pharmacological: Number of participants with adverse events	12 weeks

Collaborators and Investigators

• Sponsor: Infectious Diseases Institute
• Collaborators: University of Dublin, Trinity College
• Investigators: Principal Investigator: Judy Orikiiriza, MMED, PhD candidate

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): April 1, 2016

Study Registration Dates

• First Submitted: February 18, 2015
• First Submitted That Met QC Criteria: April 15, 2015
• First Posted (Estimate): April 20, 2015

Study Record Updates

• Last Update Posted (Estimate): April 20, 2015
• Last Update Submitted That Met QC Criteria: April 15, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Child Nutrition Disorders
• Other Study ID Numbers: ST/0110/15 (Registry Identifier: Nutrition Study Pead.)