Pathogenesis and Management of M. Ulcerans Disease, Buruli Ulcer

NCT02153034 | Unknown

• 1 other identifier: MR/J01477X/1
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 3

Brief Summary

Buruli ulcer is a neglected tropical disease caused by infection with Mycobacterium ulcerans (Mu) in rural parts of West Africa. It causes large skin ulcers mainly in children aged 5 to 15 years. Access to treatment is limited and many cases present late. There have been major advances in understanding the mechanism of disease together with improved diagnosis and management. The aim of the proposed studies is to identify markers predictive of a rapid response to antibiotic treatment and to investigate the pathogenesis of paradoxical reactions and oedematous lesions in Mu disease. Infection with Mu results in a nodule under the skin which enlarges and breaks down to form an ulcer. This is because Mu produces a toxin that spreads outwards and damages subcutaneous tissue. In recent years it has been found that antibiotic treatment for 8 weeks with daily tablets and intramuscular injections heals ulcers. This is unpleasant and it would be better if the treatment could be shortened. Our previous studies suggest this may be possible. Therefore a wide range of tests will be investigated in order to identify markers for people in whom the infection is at an early stage with low numbers of Mu bacteria and low levels of toxin in the skin. During antibiotic treatment the rate of healing will be measured to find out which markers are the most reliable. In some patients new areas of inflammation develop despite treatment and this is called a paradoxical reaction. The immune response to Mu will be investigated serially during antibiotic treatment to investigate the cause of paradoxical reactions. About 15% of patients have oedematous disease, the most severe form of Buruli ulcer. We will study the amount of Mu toxin produced by the strain of Mu cultured from patients with this form of the disease. Hypothesis

• Buruli ulcer patients that heal rapidly/slowly or develop paradoxical reactions with treatment will have associated predictive viability or serum biomarkers.
• Buruli ulcer patients with oedematous disease are associated with larger amounts of mycolactone and viable organisms

Conditions

Buruli Ulcer; Mycobacterium Ulcerans Disease

Keywords

Buruli ulcer; Mycobacterium ulcerans disease; M. ulcerans disease

Outcome Measures

Primary Outcomes (1)

• Measurement of serum/plasma proteins in diseased and healthy subjects

  Assessed for diseased participants at baseline, 8, 12, 16 weeks and only at baseline for healthy subjects

Secondary Outcomes (1)

• Viable M. ulcerans and bacterial load measurement in tissue of diseased subjects

  Assessed at baseline, 4, 8, 12, 16 only if lesions are not healed

Other Outcomes (2)

• Mycolactone measurement in tissue of diseased subjects

  Assessed at baseline, 4, 8, 12, 16 only if lesions are not healed

• Rate of healing and time to healing in diseased subjects

  The primary outcome measure will be assessed for each participant at the time of healing which will vary for participants

Study Arms (2)

Buruli ulcer patients, no intervention

Buruli ulcer patients administered standard standard care by the attending physician

Healthy contacts, no intervention

Healthy volunteers who will be contacts of patients recruited or non-endemic controls. No intervention will be administered

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with confirmed Buruli ulcer and healthy contacts of patients with Buruli ulcer

You may qualify if:

• All patients 5 years old or more diagnosed as having Buruli ulcer.
• Age-matched household contacts of patients that present with Buruli ulcer and healthy volunteers living in Buruli ulcer non-endemic communities

You may not qualify if:

• Patients aged less than 5 years and those
• Unwilling to give informed consent

Sponsors & Collaborators

• Kwame Nkrumah University of Science and Technology: lead

Study Sites (3)

Tepa Government Hospital

Tepa, Ahafo Ano North District, Ghana

Location

Agogo Presbyterian Hospital

Agogo, Asante Akim North District, Ghana

Location

Nkawie Government Hospital

Nkawie, Atwima Nwabiangya District, Ghana

Location

Related Publications (1)

• Frimpong M, Agbavor B, Duah MS, Loglo A, Sarpong FN, Boakye-Appiah J, Abass KM, Dongyele M, Amofa G, Tuah W, Frempong M, Amoako YA, Wansbrough-Jones M, Phillips RO. Paradoxical reactions in Buruli ulcer after initiation of antibiotic therapy: Relationship to bacterial load. PLoS Negl Trop Dis. 2019 Aug 26;13(8):e0007689. doi: 10.1371/journal.pntd.0007689. eCollection 2019 Aug.

  PMID: 31449522 DERIVED

MeSH Terms

Conditions

Buruli Ulcer

Condition Hierarchy (Ancestors)

Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Richard O Phillips, FWACP,FGCP

  Kwame Nkrumah University of Science and Technology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: May 28, 2014
• First Posted: June 2, 2014
• Study Start: May 1, 2013
• Primary Completion: December 15, 2016
• Study Completion: January 1, 2018
• Last Updated: March 23, 2017

Record last verified: 2017-03

Locations

GH (3)