Severe and Cerebral Malaria Investigated Through Host Metabolomics

June 19, 2018 updated by: University of Oxford

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

  • 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

840

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bangladesh
      • Chittagong, Bangladesh
        • Chittagong Medical College Hospital (CMCH)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

In total, up to 840 patients may be enrolled in this study.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Severe/Cerebral Malaria
Intensive monitoring
Other: Observation
Uncomplicated Malaria
Intensive monitoring
Other: Observation
Sepsis
Intensive monitoring
Other: Observation
Acidosis
Intensive monitoring
Other: Observation
Encephalitis
Intensive monitoring
Other: Observation
Healthy Individuals
Monitoring
Other: Observation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterisation of patterns of metabolic dysregulation in severe malaria
Time Frame: 4-6 weeks
Interrelationship between disturbances in metabolic pathways associated with acidosis and cerebral malaria
4-6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

Chittagong Medical College and Hospital

Investigators

  • Principal Investigator: Prof. Arjen M. Dondorp, MD, Mahidol Oxford Tropical Medicine Research Unit

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2015

Primary Completion (Actual)

September 1, 2017

Study Completion (Actual)

September 1, 2017

Study Registration Dates

First Submitted

May 15, 2015

First Submitted That Met QC Criteria

May 19, 2015

First Posted (Estimate)

May 22, 2015

Study Record Updates

Last Update Posted (Actual)

June 20, 2018

Last Update Submitted That Met QC Criteria

June 19, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BAKMAL1407

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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