Clinical trial NCT03634488: Management of Severe Acute Malnutrition in SCD, in Northern Nigeria
Official title: Management of Severe Acute Malnutrition in Children With Sickle Cell Disease Greater Than 5 Years of Age Living in Northern Nigeria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sickle Cell Anemia
Severe Acute Malnutrition
Keywords: sickle cell disease
sub-Saharan Africa
malnutrition
low-income settings
severe acute malnutrition
sickle cell anemia
Nigeria
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: Aminu Kano Teaching Hospital
name: Murtala Muhammad Specialist Hospital
First posted: 2018-08-16
Enrollment: 132
Sex: ALL
Minimum age (years): 5
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A 12-week, open label, randomized controlled feasibility trial in children with sickle cell anemia between 5 and 12 years of age to treat uncomplicated severe malnutrition.
Primary purpose: TREATMENT

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 nutrition feasibility trial is to identify whether families of children with sickle cell disease (SCD) 5 years and older 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 and older with and without SCD, in a low-resource setting.

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) 5 years and older. 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 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 ready-to-use therapeutic food and moderate fixed-dose hydroxyurea therapy is superior to ready-to-use therapeutic food alone, the investigators will randomly allocate up to 150 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 SCD 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.

Eligibility 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, 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.

Primary outcomes:
measure: Enrollment Rate at the End of the 6-month Recruitment Period
timeFrame: 6 months
measure: Retention Over 12-week Period
timeFrame: 12 weeks
measure: Percentage of Ready-to-use Therapeutic Food Sachets Returned as Empty.
timeFrame: 12 weeks
measure: Number of Missed Visits
timeFrame: 12 weeks
measure: Percentage of Hydroxyurea Pills Returned
timeFrame: 12 weeks
measure: Change in Mean Corpuscular Volume
timeFrame: 12 weeks
measure: Change in Fetal Hemoglobin Level Percentage
timeFrame: Baseline to 12 weeks
measure: Mean Corpuscular Volume Values at Exit
timeFrame: Feasibility over 12-week Period [Time Frame: 3 months]
measure: Fetal Hemoglobin Levels at Exit
timeFrame: Feasibility over 12-week Period [Time Frame: 3 months]
measure: Total Hemoglobin Levels at Exit
timeFrame: Feasibility over 12-week Period [Time Frame: 3 months]
Secondary outcomes:
measure: Percentage of Participants Maintaining a BMI Z-score Less Than -3.0
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Kano
country: Nigeria
facility: Aminu Kano Teaching Hospital
city: Kano
country: Nigeria
facility: Murtala Mohammad Specialist Hospital
Study officials:
affiliation: Vanderbilt University Medical Center
name: Michael DeBaun
role: PRINCIPAL_INVESTIGATOR
References: