Tuberculosis Clinical Trial
Official title:
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.
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.
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