Active clinical trials for "Malaria, Cerebral"

The initial study to be conducted under this IND is a 3-arm dose escalation study. The first two arms will be open-label, dose escalation, and will define the safety of 6-diazo-5-oxo-L-norleucine (DON) in African adults (>18 years old), who are healthy or who have uncomplicated malaria. Each of the two adult arms will enroll 40 participants broken down into 4 dosage groups with safety evaluations before each dose increase. The first 10 participants enrolled will receive 0.1 mg/kg intravenous (IV) DON. If this dose is proven safe, the dose will be increased to 1.0 mg/kg IV DON, and then 5.0 mg/kg IV DON, and then the final group will receive 10.0 mg/kg IV DON. Each adult dosage group contains 10 healthy participants and 10 participants with uncomplicated malaria. The total number of adult participants enrolled is 80 (20 participants at 4 doses). All participants will receive only one dose of DON. Adult participants will receive a premedication dose of the antiemetic ondansetron, 8 mg IV, administered 30 minutes prior to DON, and repeated once 6 hours later. The duration of study participation for all adult participants is six months. Once the safety profile in adults is completed, the third arm will be a randomized, placebo-controlled, dose-escalation study in children ages 6 months to 14 years with cerebral malaria to determine safety. Pediatric enrollments will span a maximum of three years (three malaria seasons, which will be carried out in Study Years 2-4), with a planned interim analysis look at the end of malaria Study Year 3 to determine dosing for malaria Study Year 4. We will first enroll 6 sentinel pediatric patients in malaria season 1 who will receive intravenous artesunate therapy and either adjunctive DON 0.1 mg/kg or placebo randomized 2:1). After review of results by the DSMB, and if approval to move forward is granted, in malaria season 2 (Study Year 3) the next year of pediatric enrollments (n=29, to account for the 6 sentinel subjects) participants will be randomized to receive one of 2 lower doses of adjunctive DON (0.1 mg/kg or 1.0 mg/kg) or placebo (24 subjects will receive DON and 5 will receive placebo) in conjunction with IV artesunate. If DON has a promising risk-benefit profile, the study will continue into a third season of pediatric enrollments (Study Year 4) (n=35) with similar or higher doses of DON (up to 10 mg/kg) or placebo in combination with IV artesunate. pediatric participation in the study will be 6 months.

This study evaluates the effectiveness of two interventions in Malawian children with cerebral malaria at high risk of death. One-third of the participants will receive treatment as usual, one-third will receive treatment as usual and be placed on a mechanical ventilator, and one-third will receive treatment as usual plus intravenous hypertonic saline.

Pediatric cerebral malaria (CM) affects more than 3 million children each year killing ~20% and leaving one third of survivors with long term neurologic and psychiatric sequelae. Seizures occur commonly with CM and are associated with an increased risk of death and neuropsychiatric disabilities. In this Malawi-based, dose- escalation, safety and feasibility study of enteral levetiracetam in pediatric CM, the investigators will lay the groundwork for future efficacy studies aimed at improving seizure control and ultimately decreasing the neurologic morbidity of pediatric CM.

Pediatric cerebral malaria (CM) affects more than 3 million children each year killing ~20% and leaving one third of survivors with long term neurologic and psychiatric sequelae. Seizures occur commonly with CM and are associated with an increased risk of death and neuropsychiatric disabilities. In this Malawi-based, safety and feasibility study of enteral levetiracetam in pediatric CM, the investigators will lay the groundwork for future efficacy studies aimed at improving seizure control and ultimately decreasing the neurologic morbidity of pediatric CM.

The purpose of this study is to assess if adding inhaled Nitric Oxide to other malaria treatments can improve the outcome of cerebral malaria in children aged 2months to 12 years.

The purpose of this study is to establish the safety, tolerability and pharmacokinetics of a single dose of the antimalarial drug artesunate.

The purpose of this study is to establish the safety, tolerability, and pharmacokinetics of a multiple dose of the antimalarial drug artesunate.

The purpose of this study is to determine whether computerised cognitive rehabilitation training improves cognition in children who have had cerebral malaria.

The impact of neurological disorders is enormous worldwide, and it is increased in poor settings, due to lack of diagnosis and treatment facilities as well as delayed management. In sub-Saharan Africa, the few observational studies conducted for the past 20 years show that neurological disorders accounted for 7 to 24% of all admissions. Central nervous system (CNS) infections were suspected in one third of all patients admitted with neurological symptoms, with a specific microbial aetiology identified in half of these. Most CNS infections may be considered as "severe and treatable diseases", e.g. human African trypanosomiasis (HAT), cerebral malaria, bacterial meningitis, CNS tuberculosis etc. If left untreated, death or serious sequels occur (mortality rates were as high as 30% in the above mentioned studies), but the outcome may be favourable with timely and appropriate management. In poor settings, such conditions should be targeted in priority in the clinical decision-making process. Unfortunately, most neuro-infections present with non-specific symptoms in their early stages, leading to important diagnostic delays. Moreover, they require advanced diagnostic technology, which is not available in most tropical rural settings: here, you have to rely on clinical judgment and first-line laboratory results, whose confirming or excluding powers are limited or unknown. Several rapid diagnostic tests (RDTs) have been recently developed for conditions like malaria or HIV, but their diagnostic contribution has not been evaluated within a multi-disease approach. Thus, this research aims at improving the early diagnosis of severe and treatable neglected and non-neglected infectious diseases which present with neurological symptoms in the province of Bandundu, Democratic Republic of Congo (DRC), by combining classic clinical predictors with a panel of simple point-of-care rapid diagnostic tests. The evaluation of existing algorithms and elaboration/validation of new guidelines will be described in a subsequent protocol.

Cerebral malaria is the most lethal complication of P.falciparum infection with a mortality rate between 5 and 40%. Intravenous quinine remains the recommended treatment for cerebral malaria. However its administration is often not feasible due to lack of simple equipment or trained staff. When referral is not possible, a viable alternative is needed. The intrarectal route is of interest in children since it is painless and simple. Studies of the efficacy of intrarectal quinine in the treatment of cerebral malaria are limited. The study aims to establish the efficacy of intrarectal quinine in the treatment of childhood cerebral malaria.