Management of Severe Acute Malnutrition in SCD, in Northern Nigeria

Sponsor
Vanderbilt University Medical Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT03634488
Collaborator
Aminu Kano Teaching Hospital (Other), Murtala Muhammad Specialist Hospital (Other)
100
3
3
15.4
33.3
2.2

Study Details

Study Description

Brief Summary

Except for children with HIV, all recommendations for treatment of childhood malnutrition are for children < 5 years of age. The overall goal of this randomized controlled nutritional feasibility trial is to identify whether families of children with sickle cell anemia (SCA) > 5 years of age agree to participate over a 12-week period. The investigators will also establish a safety protocol for monitoring potential complications associated with treating severe malnutrition in children > 5 years of age with and without SCA, in a low-resource setting.

Condition or Disease Intervention/Treatment Phase
  • Drug: hydroxyurea (20mg/kg/day)
  • Dietary Supplement: Nutritional Supplement
Phase 2

Detailed Description

The overall goal of this feasibility trial is to determine the acceptability of a randomized controlled trial to ascertain the optimal strategy for the treatment of severe malnutrition in children with sickle cell disease (SCD) older than 5 years of age. No international standard or evidence-based guidelines exist for the treatment of severe malnutrition (defined as BMI Z-score below -3) in children with SCD. With an expanding pediatric population of more than 75 million in Nigeria, coupled with decreasing childhood infectious disease-related mortality, the next emerging threats to preventable childhood deaths are non-communicable diseases. Data from our ongoing NIH-funded randomized controlled primary stroke prevention trial in Nigeria (NCT02560935), in which the investigators evaluated children with SCD between 5 and 12 years of age, demonstrated that 29% (230/803) of the cohort met criteria for severe malnutrition. Approximately 92% of the cohort in northern Nigeria identified as having severe malnutrition was below the 5th percentile for weight of children with SCD living in the US, Canada, or Europe. These data indicate older children with SCD living in northern Nigeria are undernourished when compared to children living with SCD in high-resource settings. A potentially unique attribute to treating malnutrition in children with SCD is the use of FDA approved anti-metabolite, hydroxyurea, to prevent vaso-occlusive pain events in children. The beneficial effects of hydroxyurea include, but are not limited to, decreased inflammation and increased hemoglobin levels. Preliminary evidence in this cohort of older children with sickle cell anemia (SCA) in northern Nigeria reveals that moderate fixed-dose hydroxyurea (20 mg/kg/day) significantly increases BMI in children with severe malnutrition. The investigators propose a randomized controlled feasibility trial in older children (5 to 12 years of age) with SCA living in northern Nigeria. In preparation for a definitive phase III trial to determine if a nutritional supplement (SoyaPlus) and moderate fixed-dose hydroxyurea therapy is superior to a nutritional supplement alone, the investigators will randomly allocate 100 children between 5 and 12 years of age with SCA and severe uncomplicated malnutrition to each of the two arms. In aim 1, the investigators will assess the feasibility (rate of recruitment, retention, and adherence) of a randomized controlled trial (RCT) in children with SCA and severe malnutrition to a 12-week intervention period. For aim 2, the investigators will establish the safety protocol to monitor for unknown rates of complications associated with treating malnutrition in children with SCD. To decrease the likelihood of sharing limited food resources in a poor family and to determine the specificity of malnutrition for children with SCD in northern Nigeria, the investigators will screen and treat up to 100 malnourished non-SCD siblings of the trial participants. After completion of this feasibility trial, the investigators will use the acquired knowledge to design a phase III trial to definitively determine the optimal treatment strategy for severe malnutrition in older children with SCD living in Africa, potentially affecting thousands of children in this region.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
A 12-week, open label, randomized controlled feasibility trial in children with SCA between 5 and 12 years of age to treat uncomplicated severe malnutrition.A 12-week, open label, randomized controlled feasibility trial in children with SCA between 5 and 12 years of age to treat uncomplicated severe malnutrition.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Management of Severe Acute Malnutrition in Children With Sickle Cell Disease Greater Than 5 Years of Age Living in Northern Nigeria
Actual Study Start Date :
Aug 18, 2021
Anticipated Primary Completion Date :
May 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Nutritional Supplement and Hydroxyurea

50 children (5-12 years old) with SCA and severe malnutrition will be randomly allocated to receive nutritional supplement and hydroxyurea (20mg/kg/day)

Drug: hydroxyurea (20mg/kg/day)
Treatment of severe malnutrition in children with SCA in northern Nigeria
Other Names:
  • hydrea
  • Dietary Supplement: Nutritional Supplement
    Treatment of severe malnutrition in children with SCA in northern Nigeria per local protocol with SoyaPlus
    Other Names:
  • SoyaPlus
  • RUTF
  • Placebo Comparator: Nutritional Supplement alone

    50 children (5-12 years old) with SCA and severe malnutrition will be randomly allocated to receive nutritional supplement alone

    Dietary Supplement: Nutritional Supplement
    Treatment of severe malnutrition in children with SCA in northern Nigeria per local protocol with SoyaPlus
    Other Names:
  • SoyaPlus
  • RUTF
  • Placebo Comparator: non-SCD AND severe malnutrition

    To decrease the likelihood of sharing limited food resources, we will enroll 100 malnourished non-SCD siblings.

    Dietary Supplement: Nutritional Supplement
    Treatment of severe malnutrition in children with SCA in northern Nigeria per local protocol with SoyaPlus
    Other Names:
  • SoyaPlus
  • RUTF
  • Outcome Measures

    Primary Outcome Measures

    1. Therapy Acceptance and Adherence over 12-week Period [4 months]

      The primary outcome measure will be adherence to daily administration of hydroxyurea and nutritional therapy. If adherence rate is less than 55%, alternative strategies must be considered for the definitive Phase III Trial.

    Secondary Outcome Measures

    1. Nutritional Safety protocol for Children with Sickle Cell Anemia and Severe Malnutrition [6 months]

      Study investigators will evaluate the use of a standard of care managament for severe malnutrition using the same protocol as World Health Organization (WHO). Study investigators expect the proportion of serious adverse reactions, as well as refeeding-related morbidity and mortality, to be very small compared to the benefits. Study investigators will compare the frequency of severe adverse events in the SCA group with children without SCD.

    2. Feasibility of a Definitive Phase III Trial for Hydroxyurea and Nutritional Therapy to Treat Severe Malnutrition in Sickle Cell Disease [6 months]

      During the course of this study, study investigators will prepare a manual of operations and case report forms for the proposed trial. Investigators will also solidify working relationships with our colleagues and collaborators at sites in Kano, Nigeria; and develop and organize all committees, collaborators and study procedures necessary for initiation of a successful, definitive, Phase III Trial

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    5 Years to 12 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • confirmed diagnoses of SCA, comparison children without SCD

    • severe malnutrition defined as a BMI z-score < -3

    • age between 5 and 12 years (assessment can take place up until the 13th birthday)

    • pass the appetite test

    • uncomplicated malnutrition (good appetite, alert, no signs of infection of respiratory distress)

    Exclusion Criteria:
    • children with complicated severe acute malnutrition

    • children with electrolyte disturbances (serum Na, K, Ca, PO4) at baseline

    • children on disease-modifying therapy (hydroxyurea or regular blood transfusion therapy)

    • children enrolled in other studies

    • children with diabetes and other chronic illnesses

    • children with known HIV infection

    • children with a known allergy to dairy or peanuts.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Vanderbilt University Medical Center Nashville Tennessee United States 37232-9000
    2 Aminu Kano Teaching Hospital Kano Nigeria
    3 Murtala Mohammad Specialist Hospital Kano Nigeria

    Sponsors and Collaborators

    • Vanderbilt University Medical Center
    • Aminu Kano Teaching Hospital
    • Murtala Muhammad Specialist Hospital

    Investigators

    • Principal Investigator: Michael DeBaun, Vanderbilt University Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Michael DeBaun, Vice Chair for Clinical Research, JC Peterson Endowed Chair, Professor of Pediatrics and Medicine, Director, Vanderbilt-Meharry-Matthew Walker Center of Excellence in Sickle Cell Disease, Vanderbilt University Medical Center
    ClinicalTrials.gov Identifier:
    NCT03634488
    Other Study ID Numbers:
    • 170577
    First Posted:
    Aug 16, 2018
    Last Update Posted:
    Dec 10, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Michael DeBaun, Vice Chair for Clinical Research, JC Peterson Endowed Chair, Professor of Pediatrics and Medicine, Director, Vanderbilt-Meharry-Matthew Walker Center of Excellence in Sickle Cell Disease, Vanderbilt University Medical Center
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 10, 2021