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Management of Severe Acute Malnutrition in SCD, in Northern Nigeria

Primary Purpose

Sickle Cell Anemia, Severe Acute Malnutrition

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
hydroxyurea (20mg/kg/day)
Ready-to-use therapeutic food
Sponsored by
Vanderbilt University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Anemia focused on measuring sickle cell disease, sub-Saharan Africa, malnutrition, low-income settings, severe acute malnutrition, sickle cell anemia, Nigeria

Eligibility Criteria

5 Years - 12 Years (Child)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Placebo Comparator

Arm Label

Ready-to-use therapeutic food and Hydroxyurea

Ready-to-use therapeutic food alone

non-SCD AND severe malnutrition

Arm Description

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

50 children (5-12 years old) with SCA and severe malnutrition will be randomly allocated to receive Ready-to-use therapeutic food alone

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

Outcomes

Primary Outcome Measures

Therapy Acceptance and Adherence over 12-week Period
The primary outcome is the proportion of eligible individuals that agree to be included, referred to as the recruitment rate, the retention rate for the trial, and the adherence rates to both the protocol and to therapy (Ready-to-use therapeutic food and hydroxyurea).

Secondary Outcome Measures

Nutritional Safety protocol for Children with Sickle Cell Anemia and Severe Malnutrition
The outcome for safety is our ability to identify serious adverse events (SAE), defined as death, ICU admission, or life-threatening infection in a timely manner and monitor such events. We will assess the percentage of children with SAEs during the study period (expressed as a point estimate ± 95% CIs), and also the rate of events (events/person year)
Feasibility of a Definitive Phase III Trial for Hydroxyurea and Nutritional Therapy to Treat Severe Malnutrition in Sickle Cell Disease
Not a secondary outcome; however as an overall objective of the study, the 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

Full Information

First Posted
January 30, 2018
Last Updated
October 4, 2023
Sponsor
Vanderbilt University Medical Center
Collaborators
Aminu Kano Teaching Hospital, Murtala Muhammad Specialist Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03634488
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 18, 2021 (Actual)
Primary Completion Date
October 5, 2022 (Actual)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center
Collaborators
Aminu Kano Teaching Hospital, Murtala Muhammad Specialist Hospital

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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 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 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 150 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Anemia, Severe Acute Malnutrition
Keywords
sickle cell disease, sub-Saharan Africa, malnutrition, low-income settings, severe acute malnutrition, sickle cell anemia, Nigeria

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
Investigator
Masking Description
Allocation was concealed from all other study personnel, except statisticians.
Allocation
Randomized
Enrollment
110 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ready-to-use therapeutic food and Hydroxyurea
Arm Type
Experimental
Arm Description
50 children (5-12 years old) with SCA and severe malnutrition will be randomly allocated to receive Ready-to-use therapeutic food and hydroxyurea (20mg/kg/day)
Arm Title
Ready-to-use therapeutic food alone
Arm Type
Placebo Comparator
Arm Description
50 children (5-12 years old) with SCA and severe malnutrition will be randomly allocated to receive Ready-to-use therapeutic food alone
Arm Title
non-SCD AND severe malnutrition
Arm Type
Placebo Comparator
Arm Description
To decrease the likelihood of sharing limited food resources, we will enroll up to 100 malnourished non-SCD siblings.
Intervention Type
Drug
Intervention Name(s)
hydroxyurea (20mg/kg/day)
Other Intervention Name(s)
hydrea
Intervention Description
Treatment of severe malnutrition in children with SCA in northern Nigeria
Intervention Type
Dietary Supplement
Intervention Name(s)
Ready-to-use therapeutic food
Other Intervention Name(s)
RUTF
Intervention Description
Treatment of severe malnutrition in children with SCA in northern Nigeria with an additional 500-1000 calories from ready-to-use-therapeautic food
Primary Outcome Measure Information:
Title
Therapy Acceptance and Adherence over 12-week Period
Description
The primary outcome is the proportion of eligible individuals that agree to be included, referred to as the recruitment rate, the retention rate for the trial, and the adherence rates to both the protocol and to therapy (Ready-to-use therapeutic food and hydroxyurea).
Time Frame
Feasibility over 12-week Period [Time Frame: 4 months]
Secondary Outcome Measure Information:
Title
Nutritional Safety protocol for Children with Sickle Cell Anemia and Severe Malnutrition
Description
The outcome for safety is our ability to identify serious adverse events (SAE), defined as death, ICU admission, or life-threatening infection in a timely manner and monitor such events. We will assess the percentage of children with SAEs during the study period (expressed as a point estimate ± 95% CIs), and also the rate of events (events/person year)
Time Frame
6 months
Title
Feasibility of a Definitive Phase III Trial for Hydroxyurea and Nutritional Therapy to Treat Severe Malnutrition in Sickle Cell Disease
Description
Not a secondary outcome; however as an overall objective of the study, the 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
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael DeBaun
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-9000
Country
United States
Facility Name
Aminu Kano Teaching Hospital
City
Kano
Country
Nigeria
Facility Name
Murtala Mohammad Specialist Hospital
City
Kano
Country
Nigeria

12. IPD Sharing Statement

Plan to Share IPD
No

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Management of Severe Acute Malnutrition in SCD, in Northern Nigeria

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