Management of Severe Acute Malnutrition in SCD, in Northern Nigeria

NCT03634488 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 170577
• Study Type: interventional
• Target: 132
• Locations: 2 countries
• Sites: 3

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.

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

Outcome Measures

Primary Outcomes (10)

• 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

• 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

• 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

• Number of Missed Visits

  Adherence to monthly visits was assessed based on the number of missed visits

  12 weeks

• 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

• Change in Mean Corpuscular Volume

  Adherence to hydroxyurea was evaluated based on change in mean corpuscular volume

  12 weeks

• 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

• 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]

• 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]

• 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 Outcomes (1)

• Percentage of Participants Maintaining a BMI Z-score Less Than -3.0

  12 weeks

Study Arms (3)

SCD - Ready-to-use therapeutic food and Hydroxyurea

EXPERIMENTAL

50-75 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)

Drug: hydroxyurea (20mg/kg/day); Dietary Supplement: Ready-to-use therapeutic food

SCD - Ready-to-use therapeutic food alone

PLACEBO COMPARATOR

50-75 children (5-12 years old) with SCA and severe malnutrition will be randomly allocated to receive ready-to-use therapeutic food alone

Dietary Supplement: Ready-to-use therapeutic food

Non-SCD siblings with severe malnutrition

PLACEBO COMPARATOR

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

Dietary Supplement: Ready-to-use therapeutic food

Interventions

hydroxyurea (20mg/kg/day) DRUG

Treatment of severe malnutrition in children with SCA in northern Nigeria

Also known as: hydrea

SCD - Ready-to-use therapeutic food and Hydroxyurea

Ready-to-use therapeutic food DIETARY_SUPPLEMENT

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

Also known as: RUTF

Non-SCD siblings with severe malnutrition; SCD - Ready-to-use therapeutic food alone; SCD - Ready-to-use therapeutic food and Hydroxyurea

Eligibility Criteria

• Age: 5 Years - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (3)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-9000, United States

Location

Aminu Kano Teaching Hospital

Kano, Nigeria

Location

Murtala Mohammad Specialist Hospital

Kano, Nigeria

Location

Related Publications (5)

• Murtala HA, Abdullahi SU, Gambo S, Kabir H, Shamsu KA, Gwarzo G, Acra SA, Stallings VA, Rodeghier M, DeBaun MR, Klein LJ. Including malnourished siblings in treatment improves nutritional outcomes for children with sickle cell anemia in Northern Nigeria: Results from a feasibility trial. Nutr Res. 2025 Dec;144:32-37. doi: 10.1016/j.nutres.2025.10.006. Epub 2025 Oct 18.

  PMID: 41253090 DERIVED

• Brechko A, Abdullahi SU, Gambo S, Murtala HA, Kabir H, Shamsu KA, Stallings VA, Rodeghier M, Ramesh A, Sellers A, Schlundt DG, DeBaun MR, Klein LJ. Adherence to ready-to-use therapeutic food in older children with sickle cell anaemia and severe acute malnutrition: a mixed-methods study in a low-income setting. BMJ Glob Health. 2025 Aug 7;10(8):e019096. doi: 10.1136/bmjgh-2025-019096.

  PMID: 40780831 DERIVED

• Ramirez-Cuebas G, Abdullahi SU, Gambo S, Murtala HA, Kabir H, Shamsu KA, Gwarzo G, Acra SA, Stallings VA, Rodeghier M, DeBaun MR, Klein LJ. Impact of Food Insecurity on Malnutrition Treatment Response in Nigerian Children With Sickle Cell Anemia and Severe Acute Malnutrition. Pediatr Blood Cancer. 2025 Jun;72(6):e31637. doi: 10.1002/pbc.31637. Epub 2025 Mar 10.

  PMID: 40062628 DERIVED

• Ritter C, Abdullahi SU, Gambo S, Murtala HA, Kabir H, Shamsu KA, Gwarzo G, Banaei Y, Acra SA, Stallings VA, Rodeghier M, DeBaun MR, Klein LJ. Impact of maternal depression on malnutrition treatment outcomes in older children with sickle cell anemia. BMC Nutr. 2024 Jan 24;10(1):18. doi: 10.1186/s40795-024-00826-0.

  PMID: 38268013 DERIVED

• Abdullahi SU, Gambo S, Murtala HA, Kabir H, Shamsu KA, Gwarzo G, Acra S, Stallings VA, Rodeghier M, DeBaun MR, Klein LJ. Feasibility trial for the management of severe acute malnutrition in older children with sickle cell anemia in Nigeria. Blood Adv. 2023 Oct 24;7(20):6024-6034. doi: 10.1182/bloodadvances.2023010789.

  PMID: 37428866 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Severe Acute Malnutrition; Malnutrition

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Limitations and Caveats

The sample size for this feasibility study was not determined with the goal of assessing differences in efficacy between the treatment arms. As a feasibility study, the sample size was not based on determining the difference in efficacy of the 2 treatment arms.

Results Point of Contact

• Title: Leshana Saint Jean
• Organization: Vanderbilt UniversityVanderbilt-Meharry Center of Excellence in Sickle Cell Disease

leshana.saint.jean@vumc.org

6158751992

Study Officials

• Michael DeBaun

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Allocation was concealed from all other study personnel, except statisticians.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: 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

Model Details: 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.

Study Record Dates

• First Submitted: January 30, 2018
• First Posted: August 16, 2018
• Study Start: August 18, 2021
• Primary Completion: October 5, 2022
• Study Completion: November 9, 2022
• Last Updated: March 27, 2024
• Results First Posted: March 27, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); NG (2)