Severe and Cerebral Malaria Investigated Through Host Metabolomics

Severe Malaria Clinical Trial

Official title:

Microvascular and Metabolic Dysregulation in the Pathogenesis of Severe and Cerebral Malaria Investigated Through Host Metabolomics

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02451904
• Other study ID #: BAKMAL1407
• Status: Completed
• Start date: June 2015
• Est. completion date: September 2017

Study information

• Verified date: June 2018
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

• The aim is to describe disease mechanisms of severe and cerebral malaria and identify new targets for adjunctive therapies.

• Despite treatment between 10-30% of patients with severe malaria die.

• Metabolic acidosis and cerebral malaria are major complications associated with mortality across all age groups. Still, their underlying pathogenesis remains incompletely understood.

• Using a metabolomics approach, this study aims to characterise the spectrum of acids accumulating during acidosis, and investigate patterns of metabolic dysregulation associated with coma and seizures.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 840
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years and older

Eligibility

Severe/Cerebral Malaria:

• Any P. falciparum parasitaemia detected by asexual stages on a peripheral blood-slide or a positive rapid diagnostic test in combination with one or more Modified WHO Criteria for Severe Malaria (Hien et al, 1996)

• < 24 hours after treatment commencement with either parenteral artemisinin or quinine

• Age > 12 years

• Full informed written consent obtained

Uncomplicated malaria:

• Any level of Plasmodium parasitaemia, detected by asexual stages on a peripheral blood-slide or a positive rapid diagnostic test without any of the complications of severe malaria stated above.

• Age > 12 years

• Full informed written consent obtained

Sepsis:

• Clinical signs of infection in combination with any two of the following signs:

1. Heart rate > 90 beats per minute;

2. Respiratory rate > 20 breaths per minute, a PaCO2 of < 32 mmHg, or the use of mechanical ventilation for an acute respiratory process;

3. Tympanic temperature > 38°C or < 36 °C;

4. White-cell count of > 12x109/L or < 4x109/L, or a differential count showing 10% immature neutrophils ;

• Negative peripheral blood slide for any stages of malaria parasites or a negative rapid diagnostic test for falciparum and vivax malaria

• [As bacterial culture is not routinely available at the study site, positivity of cultures is not required]

• Age > 12 years

• Full informed written consent obtained

Acidosis:

• Clinical suspicion of metabolic acidosis in combination with any of the following:

1. Peripheral venous bicarbonate < 15 mmol/L

2. Peripheral venous base excess < -3 mmol/L

• Negative peripheral blood slide for any stages of malaria parasites or a negative rapid diagnostic test for falciparum and vivax malaria; and not meeting any of the inclusion criteria for sepsis as stated above.

• Age > 12 years

• Full informed written consent obtained

Encephalitis:

• GCS < 11/15

• Documented fever > 38°C

• Onset of symptoms < 2 weeks, with an indication a lumbar puncture as part of the diagnostic work up

• Negative peripheral blood slide for any stages of malaria parasites or a negative rapid diagnostic test for falciparum and vivax malaria

• Age > 12 years

• Full informed written consent obtained

Healthy volunteers:

• No chronic or acute disease

• No fever in the past 2 weeks

• Age > 16 years

• Full informed written consent obtained

Exclusion Criteria:

• Known pre-existing chronic medical conditions including advanced hepatic disease.

Related Conditions & MeSH terms

• Malaria
• Malaria, Cerebral
• Severe Malaria

Intervention

Other:
• Observation

Locations

Country	Name	City	State
Bangladesh	Chittagong Medical College Hospital (CMCH)	Chittagong

Sponsors (2)

Lead Sponsor	Collaborator
University of Oxford	Chittagong Medical College and Hospital

Country where clinical trial is conducted

Bangladesh, 

References & Publications (2)

Dondorp A, Nosten F, Stepniewska K, Day N, White N; South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) group. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet. 2005 Aug 27-Sep 2;366(9487):717-25. — View Citation

Dondorp AM, Fanello CI, Hendriksen IC, Gomes E, Seni A, Chhaganlal KD, Bojang K, Olaosebikan R, Anunobi N, Maitland K, Kivaya E, Agbenyega T, Nguah SB, Evans J, Gesase S, Kahabuka C, Mtove G, Nadjm B, Deen J, Mwanga-Amumpaire J, Nansumba M, Karema C, Umulisa N, Uwimana A, Mokuolu OA, Adedoyin OT, Johnson WB, Tshefu AK, Onyamboko MA, Sakulthaew T, Ngum WP, Silamut K, Stepniewska K, Woodrow CJ, Bethell D, Wills B, Oneko M, Peto TE, von Seidlein L, Day NP, White NJ; AQUAMAT group. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet. 2010 Nov 13;376(9753):1647-57. doi: 10.1016/S0140-6736(10)61924-1. Epub 2010 Nov 7. Erratum in: Lancet. 2011 Jan 8;377(9760):126. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Characterisation of patterns of metabolic dysregulation in severe malaria	Interrelationship between disturbances in metabolic pathways associated with acidosis and cerebral malaria	4-6 weeks