MalariaPhase 1NCT00791531
Assessment of Safety and Pharmacokinetics of a Low Dose of Methotrexate in Healthy Adult Male Kenyan Volunteers
A Phase 1 study testing Methotrexate in people with Malaria, run by KEMRI-Wellcome Trust Collaborative Research Program at 1 site in Kenya.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- Methotrexate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteKenya
- Study dates
- Mar 2009to Aug 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males, Aged > 18 -< 55years old; weighing 55-75 kg
- Serum haemoglobin >10g/dl
- HIV negative status
- Written informed consent from the study subject.
Who cannot join
- Severe underlying conditions such as malnutrition (W/H <70%), clinically suspected cardiac, renal, or hepatic diseases, suspected AIDS, or severe injury.
- Presence of any concomitant illnesses such malaria, lower respiratory tract infections (LRTI), acute bloody or non-bloody diarrhoeas, or other as acute infections
- History of treatment with antimalarial drugs within the last 2 weeks
- History of treatment with aspirin or any non-steroidal-anti-inflammatory agent or trimethoprim and co-trimoxazole within the last 7 days.
- Any ongoing medication.
- Abnormal clinical chemistry or haematological finding
- Alcohol/drugs intake
- Any other reason in the recruiting clinician's opinion that makes the individual unsuitable for taking part in a clinical trial.
Trial locations and contacts
1 site in 1 country.
Kenya1 site
Kenya Medical Research Institute, Center for Clinical Research
Nairobi, Nairobi County, 00200
About this study
Official title: Phase 1 Assessment of Safety and Pharmacokinetics of a Low Dose of Methotrexate in Healthy Adult Male Kenyan Volunteers
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.
Read the 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.
- Conditions
- Malaria
- Being tested
- Methotrexate
- Keywords
- Methotrexate, Malaria
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethotrexateDrug
Also called Methotrexate Lerdele
Oral methotrexate 5mg once daily for 5 consecutive days
| Study group | Role | What they receive |
|---|---|---|
| Methotrexate | Experimental | Oral methotrexate 5mg once daily for 5 consecutive days Receives: Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical safety parameters:oral ulcers, GI tract disturbance,hematology, renal hepatic & other unsolicited safety AEs
Measured: 42 days
Secondary outcomes (1)
Pharmacokinetics of Methotrexate assessed by repeated measurement of blood concentrations
Measured: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2008 (estimated)
- Study startMar 2009
- Primary completionAug 2009
- Study completionAug 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- KEMRI-Wellcome Trust Collaborative Research Program
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford
- Responsible party
- Sponsor
- Investigators
- Alexis Nzila, Msc, Principal investigator, KEMRI-Wellcome Trust Collaborative Research Program
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00791531
- Sponsor's protocol ID
- SSC1464
- Status last verified
- Apr 2012
- First submitted
- 13 Nov 2008
- Last updated
- 24 Apr 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Chilengi R, Juma R, Abdallah AM, Bashraheil M, Lodenyo H, Nyakundi P, Anabwani E, Salim A, Mwambingu G, Wenwa E, Jemutai J, Kipkeu C, Oyoo GO, Muchohi SN, Kokwaro G, Niehues T, Lang T, Nzila A. A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers. Malar J. 2011 Mar 16;10:63. doi: 10.1186/1475-2875-10-63.
PubMed 21410944
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Assessment of Safety and Pharmacokinetics of a Low Dose of Methotrexate in Healthy Adult Male Kenyan Volunteers
- ClinicalTrials.gov ID
- NCT00791531
- Acronym / sponsor ID
- SSC1464
- Conditions
- Malaria
- Keywords
- Methotrexate, Malaria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- KEMRI-Wellcome Trust Collaborative Research ProgramUniversity, hospital or other
- Collaborators
- University of Oxford
- Study start
- Mar 2009
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 14 Nov 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Methotrexate | Experimental | Drug: MethotrexateOral methotrexate 5mg once daily for 5 consecutive days |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Males, Aged > 18 -< 55years old; weighing 55-75 kg
- Serum haemoglobin >10g/dl
- HIV negative status
- Written informed consent from the study subject.
Key exclusion criteria (8 listed)
- Severe underlying conditions such as malnutrition (W/H <70%), clinically suspected cardiac, renal, or hepatic diseases, suspected AIDS, or severe injury.
- Presence of any concomitant illnesses such malaria, lower respiratory tract infections (LRTI), acute bloody or non-bloody diarrhoeas, or other as acute infections
- History of treatment with antimalarial drugs within the last 2 weeks
- History of treatment with aspirin or any non-steroidal-anti-inflammatory agent or trimethoprim and co-trimoxazole within the last 7 days.
- Any ongoing medication.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethotrexateAlso: Methotrexate LerdeleOral methotrexate 5mg once daily for 5 consecutive days | Drug | Methotrexate |
Primary outcome
Clinical safety parameters:oral ulcers, GI tract disturbance,hematology, renal hepatic & other unsolicited safety AEs
Time frame: 42 days
1 secondary outcome
Pharmacokinetics of Methotrexate assessed by repeated measurement of blood concentrations
Time frame: 42 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2012.
- Results publication: PubMed 21410944Chilengi R, Juma R, Abdallah AM, Bashraheil M, Lodenyo H, Nyakundi P, Anabwani E, Salim A, Mwambingu G, Wenwa E, Jemutai J, Kipkeu C, Oyoo GO, Muchohi SN, Kokwaro G, Niehues T, Lang T, Nzila A. A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers. Malar J. 2011 Mar 16;10:63. doi: 10.1186/1475-2875-10-63.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexis Nzila, Msc principal investigator
KEMRI-Wellcome Trust Collaborative Research Program
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Methotrexate in people with Malaria, run by KEMRI-Wellcome Trust Collaborative Research Program at 1 site in Kenya.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical safety parameters:oral ulcers, GI tract disturbance,hematology, renal hepatic & other unsolicited safety AEs (time frame: 42 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00791531, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2012.