P. Falciparum Infection Dynamics and Transmission to Inform Elimination (INDIE-1b)

March 25, 2022 updated by: London School of Hygiene and Tropical Medicine
In the current study, three experimental approaches aiming at reducing malaria transmission will be tested. The study will cover two transmission season (2019 and 2020) and the interventions will vary by season. More specifically, in the 2019 transmission season (June-December) (Year 1), community case management of malaria (CCM) will be implemented in all eight villages as improved standard of care; in the 2020 transmission season (Year 2), the eight study villages will be divided into 4 study arms. CCM will continue in all villages; two villages will continue with CCM only (Arm 1, control); the three other pairs of villages will receive active fever screening and treatment (Arm 2); monthly mass screening and treatment (MSAT) (Arm 3); and mass drug administration (MDA) during the last 3 months of the dry season (April-June) (Arm 4). For MDA, the whole population (except for those not fulfilling the entry criteria) will be treated with a full course of dihydroartemisinin-piperaquine (DP) (320/40mg and 160/20mg piperaquine/ dihydroartemisinin per tablet) per manufacturer's guidelines (once daily for 3 days and according to body weight). The MDA treatment will be repeated 3 times at monthly intervals.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In the current study, the investigators will first improve access to care in all villages by implementing community-based clinical case management (CCM) (year 1). In this year, the investigators will quantify gametocyte carriage and transmission from clinical cases passively recruited by CCM, and gametocyte carriage and transmission from asymptomatic infections detected in community surveys. These data will support the interpretation of the main study outcomes in year 2 when the investigators will directly compare the effect of CCM on the human reservoir of infection as compared to three different approaches, namely i) active fever screening and treatment that should detect symptomatic infections for early treatment; ii) Mass Screening and Treatment (MSAT) that will systematically screen, using point-of-care diagnostics, the whole population, with infected individuals immediately treated; and iii) mass drug administration (MDA) that will treat the whole population with a full course of an antimalarial treatment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
4000

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Gambia
      • Basse Santa Su, Gambia
        • Recruiting
        • Medical research Council Unit The Gambia at LSHTM
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

6 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Resident in the village.
  2. Willingness to participate in repeated assessments of health and infection status and to donate a maximum of 30 mL (milliliter) of blood (children <5 years of age), 37 mL (milliliter) of blood (children <10 years of age) or 52 mL (milliliter) of blood (older individuals) during an 18-month period.

Exclusion Criteria:

  1. Any chronic illness that would affect study participation.
  2. Pre-existing severe chronic health conditions
  3. History of intolerance to artemether-lumefantrine.
  4. Participants < 6months old and pregnant women in the first trimester (only for Arm with MDA-DP treatment).
  5. Hypersensitivity to DP (only for Arm with MDA-DP treatment).
  6. Taking drugs that influence cardiac function or prolong QTcorrected interval (only for Arm with MDA-DP treatment).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
No Intervention: CCM:Standard of Care
Community Case Management (CCM), with passively monitored malaria incidence by community health workers using standard RDTs and artemisinin-based combination therapy (ACT), artemether-lumefantrine (AL) according to national guidelines.
Experimental: CCM plus weekly fever screening and treatment
CCM plus active case detection (ACD) by fever screening and treatment if positive. Trained village health workers (VHW) recruited for this study will carry out weekly visits of all residents and screen for fever using research-grade thermometers. A standard RDT will be performed in all individuals with a body temperature ≥37.5°C or with reported fever in the last 24 hours. RDT positive individuals will be treated with AL according to national guidelines.
Other: Community Case Management
Community Case Management (CCM), consisting of community health workers able to diagnose malaria by standard RDTs and treating positive individuals with artemether-lumefantrine (AL), according to national guidelines.
Other: Weekly fever screening and treatment
Consists of weekly visits by trained VHW who will screen for fever by taking the axillary temperature. If the body temperature is ≥37.5°C, a standard RDT will be performed and, if positive, the individual will be treated with AL, according to national guidelines.
Experimental: CCM plus MSAT
CCM plus monthly screening for malaria infection and treatment of positive individuals, regardless of symptoms. Screening will be performed by research staff and timed to ensure a gap of 25-35 days between screening rounds; Positive individuals will be treated with AL, according to national guidelines.
Other: Community Case Management
Community Case Management (CCM), consisting of community health workers able to diagnose malaria by standard RDTs and treating positive individuals with artemether-lumefantrine (AL), according to national guidelines.
Other: Monthly malaria screening
CCM plus monthly screening of the whole population with high sensitive RDT (HS-RDT); positive individuals will be treated with AL regardless of symptoms (MSAT).
Experimental: CCM plus dry season MDA
CCM plus plus 3 monthly rounds of MDA with a long-acting ACT (dihydroartemisinin-piperaquine, DP) starting in the dry season (April, May, June) (tablets of 320/40mg and 160/20mg piperaquine/ dihydroartemisinin per tablet. Administration of a full course of DP will be done as per manufacturer's guidelines once daily for 3 days and according to body weight).
Other: Community Case Management
Community Case Management (CCM), consisting of community health workers able to diagnose malaria by standard RDTs and treating positive individuals with artemether-lumefantrine (AL), according to national guidelines.
Other: MDA
CCM plus 3 monthly rounds of MDA with dihydroartemisinin-piperaquine (DP) starting during the dry season, before the malaria transmission season starts.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Parasite prevalence by molecular detection at the end of study (cross-sectional survey).
Time Frame: 16 weeks
The primary outcome measure is parasite prevalence in the cross-sectional survey conducted at the end of the transmission season of year 2.
16 weeks
Parasite density by molecular detection at the end of study (cross-sectional survey).
Time Frame: 16 weeks
The primary outcome measure is parasite density (parasite/µL) in the cross-sectional survey conducted at the end of the transmission season of year 2.
16 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Gametocyte prevalence by molecular methods at the end of study (cross-sectional survey).
Time Frame: 16 weeks
Gametocyte prevalence in quantitative polymerase chain reaction (qPCR) detected infections is assessed by molecular methods and compared between arms.
16 weeks
Gametocyte density by molecular methods at the end of study (cross-sectional survey).
Time Frame: 16 weeks
Gametocyte density (gametocytes/µL) in qPCR detected infections is assessed by molecular methods and compared between arms.
16 weeks
Gametocyte prevalence of male and female gametocytes by molecular methods among P. falciparum infections at all study visits.
Time Frame: Throughout study, an average of 18 months
Gametocyte prevalence of male and female gametocytes will be assessed by molecular methods and compared between study arms.
Throughout study, an average of 18 months
Gametocyte density of male and female gametocytes by molecular methods among P. falciparum infections at all study visits.
Time Frame: Throughout study, an average of 18 months
Gametocyte density of male and female gametocytes will be assessed by molecular methods and compared between study arms.
Throughout study, an average of 18 months
Incidence of malaria infections
Time Frame: Throughout study, an average of 18 months
Regular visits by weekly active case detection and monthly screening will result in the identification of malaria infections that are not detected during CCM. Number of infections detected in each arm will be quantified and compared between arms.
Throughout study, an average of 18 months
Infectivity of P. falciparum infections to mosquitoes
Time Frame: Throughout study, an average of 18 months
For a selection of infections, infectiousness to mosquitoes is assessed by membrane feeding assays.
Throughout study, an average of 18 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The detectability of infections by highly-sensitive rapid diagnostic tests related to histidine rich protein-2 (HRP2) concentrations.
Time Frame: Throughout study, an average of 18 months
For a selection of samples, the detectability of infections is assessed by highly sensitive rapid diagnostic tests related to histidine rich protein-2 (HRP2) concentrations.
Throughout study, an average of 18 months
The detectability of infections by highly-sensitive rapid diagnostic tests related to duration of infection.
Time Frame: Throughout study, an average of 18 months
For a selection of samples, the detectability of infections is assessed by highly sensitive rapid diagnostic test and related to duration of infection.
Throughout study, an average of 18 months
The detectability of infections by rapid diagnostic tests related to duration of infection.
Time Frame: Throughout study, an average of 18 months
For a selection of samples, the detectability of infections is assessed by conventional rapid diagnostic tests and related to duration of infection.
Throughout study, an average of 18 months
The detectability of infections by highly-sensitive rapid diagnostic tests related to parasite density by molecular diagnostics.
Time Frame: Throughout study, an average of 18 months
The detectability of infections is assessed by highly sensitive rapid diagnostic test and related to parasite density by molecular diagnostics.
Throughout study, an average of 18 months
The detectability of infections by rapid diagnostic tests related to parasite density by molecular diagnostics.
Time Frame: Throughout study, an average of 18 months
For a selection of samples, the detectability of infections is assessed by conventional rapid diagnostic test and related to parasite density by molecular diagnostics.
Throughout study, an average of 18 months
The relationship between the proportion of infected mosquitoes (Direct Membrane Feeding Assay) and gametocyte density.
Time Frame: Throughout study, an average of 18 months
Gametocyte density will be assessed by molecular methods and associated with infectivity mosquitoes.
Throughout study, an average of 18 months
The relationship between the proportion of infected mosquitoes (Direct Membrane Feeding Assay) and gametocyte sex-ratio.
Time Frame: Throughout study, an average of 18 months
Sex-ratio gametocytemia of P. falciparum will be assessed by molecular methods and associated with infectivity in mosquitoes.
Throughout study, an average of 18 months
The effect of infection characteristics (clonal parasite infection) on the transmissibility of infections to mosquitoes.
Time Frame: Throughout study, an average of 18 months
To determine the impact of duration and complexity of malaria infections on the transmissibility of infections to mosquitoes
Throughout study, an average of 18 months
Gametocyte sex-ratio on the transmissibility of infections to mosquitoes.
Time Frame: Throughout study, an average of 18 months
To determine the impact of gametocyte sex-ratio on the transmissibility of infections to mosquitoes
Throughout study, an average of 18 months
The impact of human haemoglobinopathies on the transmissibility of infections to mosquitoes.
Time Frame: Throughout study, an average of 18 months
To determine the impact of red blood cell haemoglobinopathies and haemoglobin concentration on the transmissibility of infections to mosquitoes.
Throughout study, an average of 18 months
Mean fluorescence intensity (MFI) to inflammatory markers and naturally acquired antibody responses to gametocyte antigens on the transmissibility of infections to mosquitoes.
Time Frame: Throughout study, an average of 18 months
To determine the impact of inflammatory markers and naturally acquired antibody responses to gametocyte antigens and other host characteristics on the transmissibility of infections to mosquitoes.
Throughout study, an average of 18 months
Relationship between total parasite density (parasite/µL) and gametocyte density (gametocytes/µL)
Time Frame: Throughout study, an average of 18 months
To assess the relationship between asexual parasite density and gametocyte density in P. falciparum infections
Throughout study, an average of 18 months
Malaria transmission potential based on measured gametocyte densities (gametocytes/µL).
Time Frame: Throughout study, an average of 18 months
To determine malaria transmission potential of infections based on the gametocyte density
Throughout study, an average of 18 months
Number of acquired parasite clones based on genotyping.
Time Frame: Throughout study, an average of 18 months
Under this outcome, we aim to examine the complexity of P. falciparum infection by measuring the number of clones present in infections
Throughout study, an average of 18 months
Number of days that P. falciparum infections last in the dry season.
Time Frame: Up to 6 months
To evaluate the duration of P. falciparum carriage during the dry season, routine follow-up will be performed.
Up to 6 months
Mosquito exposure monitored by monthly CDC-light traps (CDC-LT) and Human landing catches (HLC) mosquito collections
Time Frame: Throughout study, an average of 18 months
For the quantification of the mosquito exposure, indoor and outdoor mosquito collections will be performed monthly during transmission and dry season.
Throughout study, an average of 18 months
Mean fluorescence intensity (MFI) antibody responses to mosquito saliva proteins during high and low transmission season.
Time Frame: Throughout study, an average of 18 months
To determine the exposure to Anopheles bites with serological markers of malaria infection.
Throughout study, an average of 18 months
Number of infections in community surveys that can be linked to a symptomatic or asymptomatic parent infection.
Time Frame: Throughout study, an average of 18 months
This outcome allow bridging mosquito feeding studies with actual transmission events in communities and at the same time quantify the relevance of infections associated with movement.
Throughout study, an average of 18 months
Number of human host from mosquito blood meal source.
Time Frame: Up to 12 months
To quantify the transmission potential of individuals by identification of human blood source by molecular typing.
Up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
London School of Hygiene and Tropical Medicine

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Radboud University Medical Center
University of California, San Francisco
Medical Research Council Unit, The Gambia
National Malaria Control Programme, The Gambia
Institute for Disease Modeling

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Teun Bousema, PhD, Radboud University Medical Centre, Nijmegen, the Netherlands
  • Principal Investigator: Chris Drakeley, PhD, London School Hygiene and Tropical medicine
  • Principal Investigator: Umberto D'Alessandro, PhD, MD, MRC Unit The Gambia @ LSHTM

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 15, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 29, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 8, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 13, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 31, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 16642
  • OPP1173572 (Other Grant/Funding Number: Bill and Melinda Gates Foundation (BMGF))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Anonymised individual participant data may be shared on a digital repository or upon reasonable request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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