Vascular Function Intervention Trial in Sickle Cell Disease

• Status: Unknown status
• Trial end date: 2017-09-01
• Target enrollment: 0
• Participant gender: All

Summary

Sickle cell disease (SCD) is the most common inherited disorder worldwide affecting 300,000 births annually, most occuring in sub-Saharan Africa (SSA) where poor detection and care result in high childhood mortality, malnutrition, illness and disability in survivors. SCD is caused by abnormal haemoglobin, the compound in red blood cells(RBC) that carries oxygen. Much of the disability in SCD may be caused by vascular damage from the breakdown of damaged RBC. Research in high-income countries has led to some effective therapies but these are currently costly and complex. The investigators will test two different formulations of an affordable, ready-to-use supplementary food (RUSF) specifically tailored for children with SCD. As well as containing energy, protein, essential fats, vitamins and minerals, the vascular RUSF (RUSFv) will be fortified with the amino-acids arginine and citrulline and be delivered with a daily chloroquine dose to create a novel "nutraceutical" intervention. Arginine is converted to nitric oxide which is essential for vascular health. Arginine levels are low in SCD because the arginine-degrading enzyme, arginase, is released from RBCs. The investigators propose that by supplying additional arginine (and citrulline which converts to arginine) and suppressing arginase activity (an action of chloroquine) the investigators can improve vascular function. Our study will test this theory, and if provision of RUSF improves growth in children with SCD.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: London School of Hygiene and Tropical Medicine
• Collaborator: Wellcome Trust
• Treatments: Chloroquine; Chloroquine diphosphate

Criteria

Inclusion Criteria:

• Aged 8-11 years old at enrolment and resident within urban Dar-es-Salaam

• Enrolled in Muhimbili Sickle Cohort and attending routine Muhimbili National Hospital sickle clinics

• Homozygous for hemoglobin S (HbSS) phenotype confirmed by electrophoresis and high performance liquid chromatography (HPLC)

Exclusion Criteria:

• >95th percentile for body mass index (BMI) for age using British 1990 growth standards

• Receiving hydroxyurea therapy or significant other long-term drug therapy

• Diagnosis with clinically significant non-SCD related disease including:

• Stage III or above HIV - or receiving ART therapy regardless of AIDS stage

• Tuberculosis infection

• Blood transfusion within previous 30 days

• Previously diagnosed clinical pulmonary hypertension or cardiac dysfunction or clinical signs of pulmonary hypertension (loud pulmonary second heart sound) or heart failure (displaced apex beat, high jugular venous pressure, enlarged liver, peripheral oedema)

• Low visual acuity at baseline (<6/9 using a modified (for Tanzania) Snellen chart or previously diagnosed chronic eye disorder likely to suggest retinopathy or macular degeneration

• Significant hepatic/renal dysfunction assessed by clinical chemistry panel at baseline

• Epilepsy, psoriasis or currently taking any drugs listed as interacting with chloroquine