MalariaNCT04666350
Clinical Investigation Study to Evaluate the Consistency and Reproducibility of Two Consecutive Mosquito Feeding Assays
An observational study of Malaria, run by PATH at 1 site in Kenya.
Trial summary
The proposed trial design has been developed to assess the consistency and reproducibility of two consecutive direct skin feeding assays (DSFA) at 24-hour interval. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Malaria
- What is being tested?
- Direct Skin Feeding Assay (DSFA), Primaquine and Artemether/Lumefantrine
- Type of treatment
- Pill or oral medicine
- How many people
- 42 participants
- Where
- 1 siteKenya
- Study dates
- 9 Mar 2021to 20 Dec 2021
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All sexes
- Adult
Study population: The target sample size for subjects with gametocytemia is approximately 45 individuals. Approximately 180 participants will be screened for gametocyte carriage by PCR to achieve the target sample size. Screening of subjects will continue until the desired sample size of gametocytemic individuals who undergo all study procedures is attained. Adults aged 18 - 55 years will be recruited from the villages in the Kombewa Health and Demographics Surveillance System (HDSS) consisting of half of Kisumu
Who may be able to join
- Provision of signed or thumb printed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female aged between 18 years and 55 years inclusive.
- Resident within the study area
- In good general health as evidenced by medical history and clinical examination before entering the study Ability to take oral Coartem and low-dose primaquine anti-malarials upon conclusion of day 2 (2nd direct skin feed) and be willing to adhere to the medication regimen
- For females, she must be of non-childbearing potential or use appropriate measures to prevent pregnancy for 30 days after receiving Coartem and primaquine. Non-childbearing potential means she is surgically sterilized or at least one year post-menopausal. Appropriate measures to prevent pregnancy include abstinence or adequate contraceptive precautions (i.e. intrauterine contraceptive device; oral contraceptives; diaphragm or condom in combination with contraceptive jelly, cream or foam; Norplant or Depo-Provera).
- For males, he must be willing to ensure that he does not get his partner(s) pregnant for at least 3 months after treatment with primaquine. Appropriate measures to prevent pregnancy include abstinence or adequate contraceptive precautions in either the participant or the partner.
- Positive for P. falciparum gametocytes as measured by polymerase chain reaction (PCR) with cycle threshold (cT) value < 31.
Who cannot join
- Presence of any signs or symptoms of malaria
- Presence of contraindications to administration of Coartem and primaquine as indicated in the respective drug package inserts
- History of severe allergic reactions to mosquito bites (other than pruritus and local swelling)
- Pregnant (i.e. a positive pregnancy test)
- Current or recent (within the preceding 2 weeks) use of antimalarial treatment
- Current participation in a malaria vaccine study
- Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Investigation Study to Evaluate the Consistency and Reproducibility of Two Consecutive Mosquito Feeding Assays in Adults With Varying Plasmodium Falciparum Gametocyte Densities
The proposed trial design has been developed to assess the consistency and reproducibility of two consecutive direct skin feeding assays (DSFA) at 24-hour interval.
Read the detailed description
The proposed trial design has been developed to assess the consistency and reproducibility of two consecutive direct skin feeding assays (DSFA) at 24-hour interval. The results will determine the type of pivotal trial design for a follow-on Phase 2b trial whose objective is to bridge the standard membrane feeding assay (SMFA) to the direct skin feeding assay (DSFA) and direct membrane feeding assay (DMFA) using a monoclonal antibody intervention, TB31F monoclonal antibody (mAb), which interrupts transmission from human to mosquito. The results from this experimental medicine study will inform whether the preferred "Before-After" trial design in which each human volunteer serves as their own internal control can be utilized for a follow-on Phase 2b trial.
- Conditions
- Malaria
- Being tested
- Direct Skin Feeding Assay (DSFA), Primaquine, Artemether/Lumefantrine
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Direct Skin Feeding Assay (DSFA)Other
In the direct feeding assay a cup with 60 unfed, sterile insectary-reared Anopheles gambiae mosquitoes will be allowed to feed on a participant's calf or arm for 15 minutes.
PrimaquineDrug
Participants will receive one dose of primaquine 26.3 mg tablet on Day 2 after completion of the direct feeding assay.
Artemether/LumefantrineDrug
Also called Coartem®
Participants will receive artemether (80 mg) and lumefantrine (480 mg) combination tablets twice a day for 3 days, starting after completion of the direct feeding assay on Day 2.
| Study group | Role | What they receive |
|---|---|---|
| Study Volunteers | Participants provided a blood sample on Day 1 for DMFA testing and then participated in the mosquito feeding assay. On Day 2 participants underwent a second DMFA and DSFA assay (within 24 hours of the first assays).
Upon completion of Day 2 DSFA participants will receive one dose of primaquine and the first dose of a 3-day regiment of artemether/lumefantrine. Receives: Other: Direct Skin Feeding Assay (DSFA); Drug: Primaquine; Drug: Artemether/Lumefantrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Oocyst Prevalence
Participants underwent feeding assays on two days, 24 hours apart (day 1 and Day 2). After feeding, mosquitoes were maintained in locked environmental chambers for 9 days to allow oocyst development.
An oocyst is a structure that develops on the outer wall of the infected mosquito's stomach that contains developing sporozoites.
Nine days after feeding mosquito midguts were dissected, stained with 1% mercurochrome and examined by optical microscopy. The number of oocysts in each midgut were recorded.
Oocyst prevalence is defined as the percentage of mosquitoes in a cup with at least one oocyst detected in the mid-gut among the surviving mosquitoes (in the same cup) that underwent the feeding assays.
Measured: Feeding assays were performed on Day 1 and Day 2; Oocyst prevalence in surviving mosquitoes was assessed 9 days after feeding (Days 9 and 10).
Secondary outcomes (3)
Oocyst Density
Participants underwent feeding assays on two days, 24 hours apart (Day 1 and Day 2). After feeding, mosquitoes were maintained in locked environmental chambers for 9 days to allow oocyst development.
An oocyst is a structure that develops on the outer wall of the infected mosquito's stomach that contains developing sporozoites.
Nine days after feeding mosquito midguts were dissected, stained with 1% mercurochrome and examined by optical microscopy. The number of oocysts in each midgut were recorded.
Oocyst density is defined as the mean number of oocysts detected in infected mosquitoes that underwent feeding assays on the same participant.
Measured: Feeding assays were performed on Day 1 and Day 2; Oocyst density in surviving mosquitos was assessed 9 days after feeding (Days 9 and 10).
Sporozoite Prevalence
Participants underwent feeding assays on two days, 24 hours apart (day 1 and Day 2). After feeding, mosquitoes were maintained in locked environmental chambers for 14 days to allow sporozoite development.
Sporozoites are the forms of the plasmodium that are liberated from the oocysts in the mosquito, accumulate in the salivary glands of the mosquito, and are transferred to humans when the mosquito feeds.
Fourteen days after feeding, salivary glands were dissected from live mosquitoes submerged in phosphate-buffered saline (PBS) in order to visualize motile sporozoites by microscopy. Sporozoite prevalence was recorded.
Sporozoite prevalence is defined as the percentage of mosquitoes in a cup with at least one sporozoite detected in the salivary glands among the mosquitoes (in the same cup) that underwent feeding assays.
Measured: Feeding assays were performed on Day 1 and Day 2; Sporozoite prevalence in surviving mosquitoes was assessed 14 days after feeding (Days 14 and 15).
Sporozoite Density
Sporozoite density is defined as the mean number of sporozoites detected in infected mosquitoes that underwent feeding assays.
Due to limitation on the state of the art, it was not possible to estimate the sporozoite density using the Optical Microscopy technique.
Measured: Day 1 and Day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2020
- Study start9 Mar 2021
- Primary completion20 Dec 2021
- Study completion20 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Collaborators
- Walter Reed Army Institute of Research (WRAIR), Kenya Medical Research Institute
- Responsible party
- Sponsor
- Investigators
- Ben Andagalu, MD, Principal investigator, Drug Resistance Laboratory, KEMRIHoseah Akala, MD, Principal investigator, Drug Resistance Laboratory, KEMRI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04666350
- Sponsor's protocol ID
- CVIA 085 -- Phase 0
- Status last verified
- Dec 2022
- First submitted
- 24 Nov 2020
- Last updated
- 29 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Akala HM, Aponte JJ, Achola MA, Juma DW, Opot BH, Maisiba RN, Okoth RO, Juma JA, Mwakio EW, Mwalo MA, Oullo DO, Abuom D, Garges EC, Eyase FL, Tina LO, Copeland NK, Roth A, Mutunga J, Onyango I, Johnson J, Ogutu BR, Sifuna P, Hutter J, Mercer L, Raine M, Moore V, Ivinson K, Wu Y, Andagalu B, Ockenhouse CF. Consistency and reproducibility of independent feedings using blood from two consecutive days at varying Plasmodium falciparum gametocyte densities based on both direct membrane feeding assay and direct skin feeding assay. Malar J. 2025 May 16;24(1):154. doi: 10.1186/s12936-025-05360-3.
PubMed 40380146
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Investigation Study to Evaluate the Consistency and Reproducibility of Two Consecutive Mosquito Feeding Assays in Adults With Varying Plasmodium Falciparum Gametocyte Densities
- ClinicalTrials.gov ID
- NCT04666350
- Acronym / sponsor ID
- CVIA 085 -- Phase 0
- Conditions
- Malaria
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Collaborators
- Walter Reed Army Institute of Research (WRAIR), Kenya Medical Research Institute
- Study start
- 9 Mar 2021 (actual)
- Primary completion
- 20 Dec 2021 (actual)
- Study completion
- 20 Dec 2021 (actual)
- First posted
- 14 Dec 2020 (actual)
- Results
- Posted 29 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed trial design has been developed to assess the consistency and reproducibility of two consecutive direct skin feeding assays (DSFA) at 24-hour interval.
Detailed description
The proposed trial design has been developed to assess the consistency and reproducibility of two consecutive direct skin feeding assays (DSFA) at 24-hour interval. The results will determine the type of pivotal trial design for a follow-on Phase 2b trial whose objective is to bridge the standard membrane feeding assay (SMFA) to the direct skin feeding assay (DSFA) and direct membrane feeding assay (DMFA) using a monoclonal antibody intervention, TB31F monoclonal antibody (mAb), which interrupts transmission from human to mosquito. The results from this experimental medicine study will inform whether the preferred "Before-After" trial design in which each human volunteer serves as their own internal control can be utilized for a follow-on Phase 2b trial.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Volunteers | – | Other: Direct Skin Feeding Assay (DSFA), Drug: Primaquine, Drug: Artemether/LumefantrineParticipants provided a blood sample on Day 1 for DMFA testing and then participated in the mosquito feeding assay. On Day 2 participants underwent a second DMFA and DSFA assay (within 24 hours of the first assays). Upon completion of Day 2 DSFA participants will receive one dose of primaquine and the first dose of a 3-day regiment of artemether/lumefantrine. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Age groups
- Adult
- Study population
- The target sample size for subjects with gametocytemia is approximately 45 individuals. Approximately 180 participants will be screened for gametocyte carriage by PCR to achieve the target sample size. Screening of subjects will continue until the desired sample size of gametocytemic individuals who undergo all study procedures is attained. Adults aged 18 - 55 years will be recruited from the villages in the Kombewa Health and Demographics Surveillance System (HDSS) consisting of half of Kisumu
Key inclusion criteria (8 listed)
- Provision of signed or thumb printed and dated informed consent form
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female aged between 18 years and 55 years inclusive.
- Resident within the study area
- In good general health as evidenced by medical history and clinical examination before entering the study Ability to take oral Coartem and low-dose primaquine anti-malarials upon conclusion of day 2 (2nd direct skin feed) and be willing to adhere to the medication regimen
Key exclusion criteria (7 listed)
- Presence of any signs or symptoms of malaria
- Presence of contraindications to administration of Coartem and primaquine as indicated in the respective drug package inserts
- History of severe allergic reactions to mosquito bites (other than pruritus and local swelling)
- Pregnant (i.e. a positive pregnancy test)
- Current or recent (within the preceding 2 weeks) use of antimalarial treatment
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 |
|---|---|---|
| Direct Skin Feeding Assay (DSFA)In the direct feeding assay a cup with 60 unfed, sterile insectary-reared Anopheles gambiae mosquitoes will be allowed to feed on a participant's calf or arm for 15 minutes. | Other | Study Volunteers |
| PrimaquineParticipants will receive one dose of primaquine 26.3 mg tablet on Day 2 after completion of the direct feeding assay. | Drug | Study Volunteers |
| Artemether/LumefantrineAlso: Coartem®Participants will receive artemether (80 mg) and lumefantrine (480 mg) combination tablets twice a day for 3 days, starting after completion of the direct feeding assay on Day 2. | Drug | Study Volunteers |
Primary outcome
Oocyst Prevalence
Time frame: Feeding assays were performed on Day 1 and Day 2; Oocyst prevalence in surviving mosquitoes was assessed 9 days after feeding (Days 9 and 10).
Participants underwent feeding assays on two days, 24 hours apart (day 1 and Day 2). After feeding, mosquitoes were maintained in locked environmental chambers for 9 days to allow oocyst development. An oocyst is a structure that develops on the outer wall of the infected mosquito's stomach that contains developing sporozoites. Nine days after feeding mosquito midguts were dissected, stained with 1% mercurochrome and examined by optical microscopy. The number of oocysts in each midgut were recorded. Oocyst prevalence is defined as the percentage of mosquitoes in a cup with at least one oocyst detected in the mid-gut among the surviving mosquitoes (in the same cup) that underwent the feeding assays.
3 secondary outcomes
Oocyst Density
Time frame: Feeding assays were performed on Day 1 and Day 2; Oocyst density in surviving mosquitos was assessed 9 days after feeding (Days 9 and 10).
Sporozoite Prevalence
Time frame: Feeding assays were performed on Day 1 and Day 2; Sporozoite prevalence in surviving mosquitoes was assessed 14 days after feeding (Days 14 and 15).
Sporozoite Density
Time frame: Day 1 and Day 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40380146Akala HM, Aponte JJ, Achola MA, Juma DW, Opot BH, Maisiba RN, Okoth RO, Juma JA, Mwakio EW, Mwalo MA, Oullo DO, Abuom D, Garges EC, Eyase FL, Tina LO, Copeland NK, Roth A, Mutunga J, Onyango I, Johnson J, Ogutu BR, Sifuna P, Hutter J, Mercer L, Raine M, Moore V, Ivinson K, Wu Y, Andagalu B, Ockenhouse CF. Consistency and reproducibility of independent feedings using blood from two consecutive days at varying Plasmodium falciparum gametocyte densities based on both direct membrane feeding assay and direct skin feeding assay. Malar J. 2025 May 16;24(1):154. doi: 10.1186/s12936-025-05360-3.
- Individual participant dataSharing planned: Undecided
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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.
Ben Andagalu, MD principal investigator
Drug Resistance Laboratory, KEMRI
Hoseah Akala, MD principal investigator
Drug Resistance Laboratory, KEMRI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malaria, run by PATH 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 8 inclusion and 7 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 29 Apr 2024. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Oocyst Prevalence (time frame: Feeding assays were performed on Day 1 and Day 2; Oocyst prevalence in surviving mosquitoes was assessed 9 days after feeding (Days 9 and 10).). 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 NCT04666350, 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 29 Apr 2024.