Zinc Supplementation in Children With Sickle Cell Disease in Western Kenya

The Effects of Zinc Supplementation in Children With Sickle Cell Disease in Western Kenya: a Pilot Study

Zinc is a nutritionally essential trace element found in previous studies to reduce growth retardation and improve immune function, which may also result in decreased incidence of infectious diseases including malaria, pneumonia and diarrhea. Sickle Cell Disease (SCD) patients are known to be susceptible to zinc deficiency and appear to benefit from zinc supplementation. The proposed pilot research project aims to investigate the influence of zinc supplementation on incidence of malaria infections, incidence of bacterial infections and investigate the influence of zinc supplementation on morbidity in children with SCD in western Kenya. The differences in incidence of morbidity and other secondary endpoints will be compared between the zinc group and the control group.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease; Zinc Deficiency; Infection
• Intervention / Treatment: Dietary supplement: Zinc Sulfate Tablets; Drug: Standard of Care

Detailed Description

Zinc is a nutritionally essential trace element found in previous studies to reduce growth retardation and improve immune function, which may also result in decreased incidence of infectious diseases including malaria, pneumonia and diarrhea. SCD patients are known to be susceptible to zinc deficiency and appear to benefit from zinc supplementation. Despite these findings, SCD patients in Kenya have not benefited from zinc supplementation programs due to a lack of research and findings to inform policy in the East African-setting. The proposed pilot research project aims to investigate the influence of zinc supplementation on incidence of malaria infections in children with SCD; investigate the influence of zinc supplementation on incidence of bacterial infections (e.g. S pneumoniae, H influenzae and non-typhi Salmonella species) in children with SCD and investigate the influence of zinc supplementation on morbidity in children with SCD in western Kenya. A 6 month randomized controlled pilot trial involving children with SCD aged 6 months to less than 13 years, being treated and followed up routinely at the KEMRI-site and other selected health facilities in Western Kenya for SCD will be enrolled. The children will be randomized into two arms, with the Intervention Group receiving the recommended Ministry of Health (MoH)/World Health Organization (WHO) standard care in addition to three times weekly zinc supplementation (10 mg) and the Control Group receiving standard MoH care alone over a six month period. At baseline, at 3 months and at 6 months, clinical and laboratory evaluations, including serum zinc levels, malaria blood slides, anthropometric measurements and other indicated laboratory tests will be conducted.The differences in incidence of morbidity and other secondary endpoints will be compared between the zinc group and the control group. The results are expected to determine the scientific basis for a larger clinical trial to determine the need for the addition of zinc supplement to the management of sickle cell disease.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female infants and children ≥ 6 months and < 13 years of age with confirmed SCD.
• Written informed consent obtained from the participant's parent/Legally Acceptable Representative (LAR).
• Available to participate for the study duration (approximately six months)

Exclusion Criteria:

• Written informed consent NOT obtained from the participant's parent/Legally Acceptable Representative (LAR).
• Profound clinical evidence of current immunosuppression or evidence of active AIDS defining illness i.e. WHO HIV clinical stage III/IV
• History of allergic reactions to zinc or any other ingredients in the supplement
• History of any neurologic disorders or seizures
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal functional abnormality, as determined by physical examination or laboratory screening tests
• Hemoglobin ≤7.0 g/dL in children aged 6 months to ≤ 2 years.
• Hemoglobin ≤ 6 g/dL in children aged >2yrs to <13 years.
• Total White Cell Count below normal range <4.5 x 103/uL
• Use of any investigational or non-registered drugs or vaccines or planned use
• Simultaneous participation in any other clinical trial
• Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zinc Sulfate Tablet; Zinc Sulfate Tablet 10 mg, 3 times a week plus Standard of Care for 6 months	Dietary supplement: Zinc Sulfate Tablets; Zinc Sulfate Tablets 3 times every 7 days for 6 months.; Other Names: Zincos; Drug: Standard of Care; Folic Acid, Proguanil, Penicillin V, Hydroxyurea over 6 months; Other Names: Folic Acid, Proguanil, Penicillin V, Hydroxyurea
Placebo Comparator: Control Arm; Standard of Care for 6 months	Drug: Standard of Care; Folic Acid, Proguanil, Penicillin V, Hydroxyurea over 6 months; Other Names: Folic Acid, Proguanil, Penicillin V, Hydroxyurea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of change in zinc levels from baseline at study conclusion.	Zinc Levels in Plasma	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of malaria episodes among recipients of zinc versus controls diagnosed by RDT or Microscopy.	Malaria Incidence	6 months
Number of episodes of bacterial infections among recipients of zinc versus controls diagnosed by culture.	Bacterial Infection Incidence	6 months
Incidence of malnutrition among recipients of zinc versus controls diagnosed based on anthropometric measurements.	Anthropometric Measurements i.e. Weight, Height and Mid Upper Arm Circumference	6 months
Occurrences of Adverse Events (AEs) during the 6 month follow-up period among recipients of zinc versus controls.	Adverse Events including Serious Adverse Events	6 months

Collaborators and Investigators

• Sponsor: Lucas Otieno Tina, MD MSc
• Collaborators: GlaxoSmithKline; Strathmore University
• Investigators: Principal Investigator: Lucas O Tina, MD MSc, KEMRI/CREATES, Strathmore University

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2016
• Primary Completion (Actual): January 19, 2017
• Study Completion (Actual): January 19, 2017

Study Registration Dates

• First Submitted: April 14, 2017
• First Submitted That Met QC Criteria: September 25, 2017
• First Posted (Actual): September 26, 2017

Study Record Updates

• Last Update Posted (Actual): September 26, 2017
• Last Update Submitted That Met QC Criteria: September 25, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Children, Sickle Cell Disease, Zinc
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites; Antineoplastic Agents; Dermatologic Agents; Micronutrients; Anti-Bacterial Agents; Vitamins; Antiprotozoal Agents; Antiparasitic Agents; Vitamin B Complex; Hematinics; Antimalarials; Antisickling Agents; Astringents; Proguanil; Hydroxyurea; Folic Acid; Zinc Sulfate; Penicillins; Penicillin V
• Other Study ID Numbers: KEMRI SSC 2925

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No