Concomitant Infections of Mansonella Perstans in Tuberculosis and Buruli Ulcer Disease Patients From Ghana
Condition: Mansonella Perstans Infection; Buruli Ulcer; Tuberculosis; Co-infection
MeSH terms: Infections; Communicable Diseases; Tuberculosis; Coinfection; Buruli Ulcer; Dipetalonema Infections; Acanthocheilonemiasis; Mansonelliasis; Ulcer
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

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.
    

Intervention name(s): Doxycycline
Intervention type(s): Drug
Intervention description(s): 200mg oral doxycycline will be administered immediately (early) in the experimental arm or delayed in the comparator arm
Other intervention name(s): Vibramycim; Oracea
Intervention MeSH terms: Doxycycline
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Coinfection; Buruli ulcer; Tuberculosis; Mansonella perstans