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Management of Severe Acute Malnutrition in SCD, in Northern Nigeria

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03634488
Recruitment Status : Active, not recruiting
First Posted : August 16, 2018
Last Update Posted : November 29, 2022
Sponsor:
Collaborators:
Aminu Kano Teaching Hospital
Murtala Muhammad Specialist Hospital
Information provided by (Responsible Party):
Michael DeBaun, Vanderbilt University Medical Center

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
Sickle Cell Anemia Severe Acute Malnutrition 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 176 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.
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 : August 18, 2021
Actual Primary Completion Date : October 5, 2022
Estimated Study Completion Date : August 2023


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 Name: 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




Primary Outcome Measures :
  1. Therapy Acceptance and Adherence over 12-week Period [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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



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Ages Eligible for Study:   5 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03634488


Locations
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United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-9000
Nigeria
Aminu Kano Teaching Hospital
Kano, Nigeria
Murtala Mohammad Specialist Hospital
Kano, Nigeria
Sponsors and Collaborators
Vanderbilt University Medical Center
Aminu Kano Teaching Hospital
Murtala Muhammad Specialist Hospital
Investigators
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Principal Investigator: Michael DeBaun Vanderbilt University Medical Center
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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: August 16, 2018    Key Record Dates
Last Update Posted: November 29, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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, Vanderbilt University Medical Center:
sickle cell disease
sub-Saharan Africa
malnutrition
low-income settings
severe acute malnutrition
sickle cell anemia
Nigeria
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Malnutrition
Severe Acute Malnutrition
Anemia
Hematologic Diseases
Nutrition Disorders
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors