Assessment of Safety and Pharmacokinetics of a Low Dose of Methotrexate in Healthy Adult Male Kenyan Volunteers
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      Previous investigations indicate that methotrexate, an old anticancer drug, could be used at
      low doses to treat malaria. This is a phase I evaluation to assess the safety and
      pharmacokinetic profile of this drug in healthy adult male Kenyan volunteers.
    

Detailed description: 
      Background Currently the control of malaria rests on the use of chemotherapy. However, the
      development of resistance to common used drugs represents a major public concern. Thus, the
      investigators need to develop new and cheap drugs. The investigators have discovered that the
      old drug methotrexate (MTX), which is used in the treatment of cancer and rheumatoid
      arthritis (RA), is very active against malaria parasites, including those that are resistant
      to existing antimalarials.

      In the treatment of RA, MTX is used weekly at a low dose for several years. At dose, MTX is
      safe and well tolerated in human and children. This low dose of MTX will also kill malaria
      parasite in human. Thus, want to study MTX as an antimalarial. As part of this study, the
      investigators need to establish whether at the dose the investigators want it, 5 mg per days
      for 5 days, the drug is safe and well tolerated in 25 Kenyan adult volunteers. This result of
      this study will inform us on the use of MTX in the treatment of malaria in children.

      What questions are the investigators trying to answer?

      The investigators are trying to assess the safety of 5mg dose per day for 5

      Where is the study taking place, how many people does it involve and how are they selected?

      The study is taking place at KEMRI, Centre for Clinical Research, Nairobi. The study will
      involve 25 healthy adults.

      What does the study involve for those who are taking part? Healthy adult males will be
      invited to join the study. A small blood sample will be collected from the arm to assess how
      the body is responding, the state of blood, liver and kidney functioning before and after the
      administration of the drug. This sample will also be used to rule out the presence of other
      infections such as HIV and Hepatitis.

      Study patients will be given MTX every day for 5 days. During the days of Hospitalization
      patients will be assessed by physical examination, and tests to check for their liver
      function on day 1 and 5. Patients will then be followed up for a minimum of 42 days and will
      be seen at the clinics on days 7, 14, 28 and 42. The state of blood, liver and kidney will be
      done only before starting treatment and on day 28. Patients will also be required to undergo
      more samples to assess the level of the drug in their blood at different times from starting
      of treatment.

      What are the benefits and risks/costs of the study for those involved Study subjects will
      receive full medical consultation and treatment through-out the study period. Long term
      benefits could be the addition of MTX to the list of antimalaria drugs available for
      treatment of non serious malaria. During the follow up period they will have the opportunity
      for their health to be followed up closely with a dedicated team of clinicians.

      MTX has been used extensively at low dose in the treatment of RA. The drug is safe and well
      tolerated in human and children. However, when used on a chronic basis, few adverse reactions
      have so far been reported, mostly gastrointestinal upsets associated with nausea and
      vomiting. The risk this sign to occur is very small since we will use the drug for 5 days
      only.

      How will the study benefit society? This study may help in development of MTX as a cheap,
      safe and easy to use drug in the treatment of malaria to add to the already available list of
      drugs.
    

Intervention name(s): Methotrexate
Intervention type(s): Drug
Intervention description(s): Oral methotrexate 5mg once daily for 5 consecutive days
Other intervention name(s): Methotrexate Lerdele
Intervention MeSH terms: Methotrexate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Methotrexate; Malaria