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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03634488
Other study ID # 170577
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date August 18, 2021
Est. completion date November 9, 2022

Study information

Verified date February 2024
Source Vanderbilt University Medical Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 132
Est. completion date November 9, 2022
Est. primary completion date October 5, 2022
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 5 Years to 12 Years
Eligibility 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.

Study Design


Intervention

Drug:
hydroxyurea (20mg/kg/day)
Treatment of severe malnutrition in children with SCA in northern Nigeria
Dietary Supplement:
Ready-to-use therapeutic food
Treatment of severe malnutrition in children with and without SCA in northern Nigeria with an additional 500-1000 calories from ready-to-use-therapeutic food

Locations

Country Name City State
Nigeria Aminu Kano Teaching Hospital Kano
Nigeria Murtala Mohammad Specialist Hospital Kano
United States Vanderbilt University Medical Center Nashville Tennessee

Sponsors (3)

Lead Sponsor Collaborator
Vanderbilt University Medical Center Aminu Kano Teaching Hospital, Murtala Muhammad Specialist Hospital

Countries where clinical trial is conducted

United States,  Nigeria, 

Outcome

Type Measure Description Time frame Safety issue
Primary Enrollment Rate at the End of the 6-month Recruitment Period Recruitment Feasibility: The primary outcome is the proportion of eligible individuals that agree to be included, referred to as the recruitment rate. Children with severe malnutrition who qualified and agreed to participate were invited to sign a consent and assent for study recruitment to this study. 6 months
Primary Retention Over 12-week Period The primary outcome is the proportion of participants who completed the 12-week trial, known as the retention rate for the trial. 12 weeks
Primary Percentage of Ready-to-use Therapeutic Food Sachets Returned as Empty. Adherence to the ready-to-use therapeutic food was evaluated based on the percentage of empty food sachets returned at each visit. 12 weeks
Primary Number of Missed Visits Adherence to monthly visits was assessed based on the number of missed visits 12 weeks
Primary Percentage of Hydroxyurea Pills Returned Adherence to hydroxyurea was evaluated based on the percentage of hydroxyurea pills returned for the group randomized to both ready-to-use therapeutic food and hydroxyurea. 12 weeks
Primary Change in Mean Corpuscular Volume Adherence to hydroxyurea was evaluated based on change in mean corpuscular volume 12 weeks
Primary Change in Fetal Hemoglobin Level Percentage The primary outcome is the proportion of eligible individuals who adhere to therapy (Ready-to-use therapeutic food and hydroxyurea). The adherence rate for hydroxyurea was determined based on the change in fetal hemoglobin level percentage. Baseline to 12 weeks
Primary Mean Corpuscular Volume Values at Exit The primary outcome is the proportion of eligible individuals who adhere to therapy (Ready-to-use therapeutic food and hydroxyurea). The adherence rate for hydroxyurea was determined based on mean corpuscular volume (MCV) values at exit (12 weeks). Feasibility over 12-week Period [Time Frame: 3 months]
Primary Fetal Hemoglobin Levels at Exit The primary outcome is the proportion of eligible individuals who adhere to therapy (Ready-to-use therapeutic food and hydroxyurea). The adherence rate for hydroxyurea was determined based on the fetal hemoglobin levels at exit (12 weeks). Feasibility over 12-week Period [Time Frame: 3 months]
Primary Total Hemoglobin Levels at Exit The primary outcome is the proportion of eligible individuals who adhere to therapy (Ready-to-use therapeutic food and hydroxyurea). The adherence rate for hydroxyurea was determined based on the total hemoglobin levels at exit (12 weeks). Feasibility over 12-week Period [Time Frame: 3 months]
Secondary Percentage of Participants Maintaining a BMI Z-score Less Than -3.0 As a secondary outcome, we assessed the percentage of participants with and without SCA who continued to have a body mass index z-score of <-3.0 at the end of the 12 weeks of treatment. Using the World Health Organization (WHO) growth reference, anthropometric measurements were converted to age and sex-specific z-scores. Anthropometric Indices (BMI-for-age (BMIZ), were calculated using WHO 2007 R Macro Package to assess growth and development of the children. Severe malnutrition/wasting (SAM) was defined as a body mass index (BMI) z-score <-3.0. 12 weeks
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