Concomitant Infections of Mansonella Perstans in Tuberculosis and Buruli Ulcer Disease Patients From Ghana (Map2Co)

March 22, 2017 updated by: Dr Richard Phillips, Kwame Nkrumah University of Science and Technology

Comparison of Early and Late Administration of Doxycycline in Their Efficacy Against Mansonella Perstans and in Development of Immunity Against Mycobacterial Infections

This study will determine the influence of doxycycline treatment against Wolbachia/M. perstans on immunity against concomitant mycobacterial infections in healthy M. perstans infected individuals. In this regard, the investigators will perform a community-based randomized controlled trial (Phase 2a) in Asante Akim North District. A cohort of 200 participants who are contacts of patients with Tuberculosis or Buruli ulcer, of both sexes with no clinical condition requiring long-term medication but connected with Mansonella perstans will be investigated for the effect of doxycycline on microfilaria, the immune response and development of mycobacterial disease.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

The purpose of this study is to describe the immune response to Mansonella perstans with or without doxycycline treatment. And to suggest the use of doxycycline for the treatment of Mansonella perstans infected individuals. Two hundred Mansonella perstans infected individuals who are contacts of patients with Buruli ulcer or Tuberculosis will be recruited and placed in two groups. Hundred patients in each group ('early', or 'delayed' doxycycline-treatment group) with weight 40kg and above. Individuals will be recruited from communities in the Asante Akim North District.

Half of the M. perstans infected individuals (randomly selected) will be treated immediately with 200mg daily doxycycline for six weeks. All recruited individuals will be asked to donate 20ml; 10 ml heparinized blood, 5ml Ethylenediaminetetraacetic acid blood and 5ml blood for serum analysis at baseline (day 0), after 4 months (day 112), after 12 months (day 336) and after 24 months (day 672). Six months after doxycycline treatment for M. perstans infected individuals the other 100 patients who are not treated at time point 0 (delayed' treatment group) will be treated as described for the 'early' treatment group. After four months (day 112) individuals from both treatment groups will be asked to donate blood for quantitative Polymerase Chain Reaction to confirm Wolbachia depletion and immunological analyses.

For 'early', and 'delayed', doxycycline-treatment group immunological assays will be performed at days 0, 112, 336 and 672 after treatment initiation for all recruited individuals.

Hypothesis:

Presence of filarial nematodes Mansonella perstans will polarize the host immunity towards humoral and T helper type 2-mediated immunity and treatment with doxycycline will result in killing of Wolbachia endosymbionts, depletion of Mansonella perstans and development of a T helper type 1 immunity and reduced risk of developing Tuberculosis and Buruli ulcer

Sample size justification Since the study is a pilot study to gain first experience regarding the primary and secondary endpoints under the intended treatment regimens, the sample size cannot be justified by a statistical argumentation. A sample size of 100 participants (80 participants plus 20% drop-out rate) per treatment arm was chosen in agreement with the study statistician.

Statistical methods The detailed plan for data analysis will be written and discussed with the DMEC before final de-blinding of the data.

Data safety Electronic data will be secured and password limited to persons named in this Study Protocol. Analyses of the data will be performed on copies of the original data files ensuring raw data accessibility at all times. Regular backups to an external hard drive will be carried out ensuring protection against data loss.

Data Monitoring and Ethics Committee (DMEC) Independent monitoring of the clinical trial will be carried out by the DMEC consisting of representatives from key stakeholders in existing filarial control programmes with the necessary expertise covering the range of project activities and skills to provide support and advice on the study progress.

Additionally the External Scientific Advisory Committee (ESAC) will monitor the study ensuring compliance with all directives. DMEC and ESAC members are listed

Informed Consent Form (ICF) Regulatory requirement necessitates obtaining and documenting informed consent, Good Clinical Practice and ethical principles along the Declaration of Helsinki (first adopted 1964, amended five times, most recently in 2000). All consent forms will accompany the study protocol and submitted for approval by the relevant ethic committees.

Patient insurance Professional indemnity liability insurance of the individual volunteers will be obtained to take care of any form of injuries that may arise in the process of drug administration.

Study Type

Interventional

Enrollment (Actual)

200

Phase

  • Phase 2

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

    • Asante Akim North District
      • Agogo, Asante Akim North District, Ghana
        • Agogo Presbyterian Hospital

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

9 years to 55 years (ADULT, CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

M. perstans mg-positive status Good general health without any clinical condition requiring long-term medication.

Normal renal and hepatic laboratory profiles

Exclusion Criteria:

Known intolerance to the doxycycline Body weight <40 kg Pregnancy or breastfeeding History of severe allergic reaction or anaphylaxis Alcohol or drug abuse

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

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Early doxycycline administered
Early doxycycline administered - volunteers will be treated immediately with 200mg daily doxycycline for 6 weeks
200mg oral doxycycline will be administered immediately (early) in the experimental arm or delayed in the comparator arm
Other Names:
  • Oracea
  • Vibramycim
ACTIVE_COMPARATOR: Delayed doxycycline administered
Delayed doxycycline administered-volunteers will be treated six months after the early group has received treatment with 200mg daily doxycycline for 6 weeks
200mg oral doxycycline will be administered immediately (early) in the experimental arm or delayed in the comparator arm
Other Names:
  • Oracea
  • Vibramycim

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microfilarial assessment
Time Frame: Change from baseline microfilarial load at 12 months
Assessment of the microfilarial load
Change from baseline microfilarial load at 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Demonstrate development of a T helper type 1 immunity through Immunological profile of cellular immune responses
Time Frame: Change from baseline T helper type 1 cytokine levels at 24 weeks
Measurement of the T helper type 1 cytokine levels
Change from baseline T helper type 1 cytokine levels at 24 weeks

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Richard Phillips O Phillips, MBChB, PhD, Kwame Nkrumah University of Science and Technology
  • Study Director: Ellis Owusu Dabo, MBChB, PhD, Kumasi Centre for Collaborative Research
  • Study Chair: Alexander Y Debrah, PhD, Kwame Nkrumah University of Science and Technology

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.

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

October 1, 2014

Primary Completion (ACTUAL)

March 15, 2017

Study Completion (ACTUAL)

March 15, 2017

Study Registration Dates

First Submitted

October 26, 2014

First Submitted That Met QC Criteria

October 30, 2014

First Posted (ESTIMATE)

November 2, 2014

Study Record Updates

Last Update Posted (ACTUAL)

March 23, 2017

Last Update Submitted That Met QC Criteria

March 22, 2017

Last Verified

March 1, 2017

More Information

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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