Sickle Cell DiseaseNCT05506358
Evaluation of Low-cost Techniques for Detecting Sickle Cell Disease and β-thalassemia in Nepal and Canada
A study testing High performance liquid chromatography, Automated sickling test and HbS solubility test in people with Sickle Cell Disease and Sickle Cell Trait, run by University of British Columbia at 3 sites in 2 countries.
Trial summary
Sickle cell disease (SCD) is an inherited blood disorder associated with acute illness and organ damage. In high resource settings, early screening and treatment greatly improve quality of life. In low resource settings, however, mortality rate for children is high (50-90%). Read more about this study
- Who is it for?
- Ages 1 year and olderHealthy volunteers can take part
- Conditions the study is for
- Sickle Cell Disease, Sickle Cell Trait, Beta-Thalassemia
- What is being tested?
- High performance liquid chromatography, Automated sickling test and HbS solubility test
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 145 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 20 Sep 2022to 30 Mar 2023
- Phase
- Interventional
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 1 year and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Since the techniques evaluated in the study aims at detecting sickle cell disease (SCD), sickle cell trait (SCT), and β- thalassemia, the following number of participants will be included in Nepal:
- 20 individuals with SCD (HbSS)
- 20 individuals with SCT (HbAS)
- 20 individuals with sickle cell/β-thalassemia compound heterozygous form (HbS/β-thalassemia)
- 20 individuals with β-thalassemia (Hbβ/β-thalassemia)
- 20 individuals with β-thalassemia trait or carrier form (HbA/β- thalassemia)
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- 20 healthy individual participants or normal participants (HbAA, participants without any known hemoglobin disorders, such as SCD, SCT or β-thalassemia)
- The following number of participants will be included in Canada:
- 30 individuals with SCD (HbSS)
- 30 individuals with SCT (HbAS)
- 30 healthy individual participants or normal participants (HbAA, participants without any known hemoglobin disorders, such as SCD, SCT or β-thalassemia)
- Participants older than 1 year of age at the time of drawing blood will be eligible. Signed and dated consent or assent forms will be required by the participants or their parents/guardians.
Who cannot join
- The exclusion criteria for the study:
- Transfusion within the last 3 months
- Pregnancy Participants who wish to withdraw from the study will also be excluded.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Canada2 sites
BC Children's Hospital
Vancouver, British Columbia, V6H 3N1
St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
About this study
Sickle cell disease (SCD) is an inherited blood disorder associated with acute illness and organ damage. In high resource settings, early screening and treatment greatly improve quality of life. In low resource settings, however, mortality rate for children is high (50-90%). Low-cost and accurate screening techniques are critical to reducing the burden of the disease, especially in remote/rural settings. The most common and severe form of SCD is sickle cell anemia (SCA), caused by the inheritance of genes causing abnormal forms of hemoglobin (called sickle hemoglobin or hemoglobin S) from both parents. The asymptomatic or carrier form of the disease, known as sickle cell trait (SCT), is caused by the inheritance of only one variant gene from one of the parents. In areas such as Nepal, β-thalassemia (another inherited blood disorder) and SCD are both prevalent, and some combinations of these diseases lead to severe symptoms.
The purpose of this study is to determine the accuracy of low-cost point-of-care techniques for screening and detecting sickle cell disease, sickle cell trait, and β-thalassaemia, which will subsequently inform on feasible solutions for detecting the disease in rural, remote, or low-resource settings. One of the goals of the study is to evaluate the feasibility of techniques, such as the sickling test with low-cost microscopy and machine learning, HbS solubility test, commercial lateral-flow assays (HemoTypeSC and Sickle SCAN), and the Gazelle Hb variant test, to supplement or replace gold standard tests (HPLC or electrophoresis), which are expensive, require highly trained personnel, and are not easily accessible in remote/rural settings.
Read more
The investigators hypothesize that:
- an automated sickling test (standard sickling test enhanced using low-cost microscopy and machine learning) has a higher overall accuracy than conventional screening techniques (solubility and sickling tests) to detect hemoglobin S in blood samples
- the automated sickling test can additionally classify SCD, SCT and healthy individuals with a sensitivity greater than 90%, based on morphology changes of red blood cells, unlike conventional sickling or solubility tests that do not distinguish between SCD and SCT cases
- Gazelle diagnostic device can detect β-thalassaemia and SCD/SCT with an overall accuracy greater than 90%, compared with HPLC as the reference test
Read the detailed description
Overall, the hypothesis is that an assessment of the performance and accuracies of low-cost point-of-care techniques (automated sickling test, solubility test, lateral-flow assays, Gazelle Hb variant test) against HPLC tests will provide researchers and health workers with feasible alternative options for screening and detecting SCD, SCT and β-thalassaemia in a variety of situations based on the needs of the communities and the resources available.
Objectives
Objectives specific to the current study are to:
- Determine accuracy (sensitivity and specificity) of automated sickling test to detect HbS, compared to gold standard HPLC, and to conventional solubility test
- Determine whether SCD, SCT and healthy individuals can be classified using the automated sickling test that leverages machine learning on images of blood films under hypoxia
- Validate accuracy (>95% sensitivity and specificity) of lateral- flow assays (HemoTypeSC and Sickle SCAN) to detect SCD/SCT, and of Gazelle variant test to detect SCD, SCT, and β-thalassaemia; and determine if low-cost techniques can potentially replace HPLC/electrophoresis tests in rural and remote settings
Long-term objectives of the overall project are to:
- Implement trained machine learning algorithm to classify SCD, SCT and healthy individuals during screening tests in Nepal
- Implement relevant low-cost point-of-care techniques in rural and remote communities of Nepal using insights and conclusions from current study
The plan of the study to screen the communities (e.g. in Nepalgunj, in Vancouver) using the following:
- Low-cost screening i. Sickling test with low-cost microscope and automated screening with machine learning ii. Sickling test with traditional microscope (conventional manual screening used in Nepal) iii. HbS solubility test iv. Commercial point-of-care assays (HemoTypeSC and Sickle SCAN) v. Gazelle Hb variant test b. Gold standard test: HPLC, for determining the accuracies of low-cost screening techniques
De-identified data (images of blood films and associated documentation) will also be deposited in an online public repository, such as the Federated Research Data Repository (FRDR). FRDR is a service of the Digital Research Alliance of Canada (Alliance), a not-for-profit organization that supports digital research infrastructure in Canada. FRDR is hosted on national infrastructure, managed and administered by the Digital Research Alliance of Canada.
- Conditions
- Sickle Cell Disease, Sickle Cell Trait, Beta-Thalassemia, Sickle Cell-Beta Thalassemia, Sickle Cell-SS Disease
- Being tested
- High performance liquid chromatography, Automated sickling test, HbS solubility test, HemoTypeSC, Sickle SCAN
- Keywords
- low-cost test, point-of-care diagnostics, automated sickling test, solubility test, HemoTypeSC, Sickle Scan, Gazelle Hb Variant Test, Machine learning, Image database, Red blood cells
- Medical subject headings
- Anemia, Sickle Cell, Sickle Cell Trait, beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High performance liquid chromatographyDiagnostic test
High performance liquid chromatography (HPLC) using the D10 System by Bio-Rad Laboratories will be used as the gold standard test.
Automated sickling testDevice
The standard sickling test using 2% sodium metabisulphite will be augmented using an automated microscope (such as Octopi) and machine learning, and will be used as one of the low-cost tests.
HbS solubility testDiagnostic test
Standard HbS solubility test currently used in Nepal (e.g. Sicklevue) will be used as one of the low-cost tests
HemoTypeSCDevice
A point-of-care lateral flow assay, HemoTypeSC (https://www.hemotype.com/), will be used as one of the low-cost tests
Sickle SCANDevice
A point-of-care lateral flow assay, Sickle SCAN (https://www.biomedomics.com/products/hematology/sicklescan/), will be used as one of the low-cost tests
Gazelle Hb Variant TestDevice
A portable electrophoresis machine, Gazelle diagnostic device (https://hemexhealth.com/), will be used as one of the low-cost tests
| Study group | Role | What they receive |
|---|---|---|
| 1) HbSS; 2) HbAS; 3) HbS/β-thalassemia; 4)Hbβ/β-thalassemia; 5) HbA/β- thalassemia; 6) HbAA | Other | Around 20 participants each (in Nepal):
* with the homozygous form of sickle cell disease (HbSS)
* with the heterozygous form of sickle cell disease (HbAS)
* with the compound heterozygous form of sickle cell disease (HbS/β-thalassemia)
* with the carrier form of β-thalassemia (HbA/β-thalassemia)
* with the carrier form of β-thalassemia (HbA/β-thalassemia)
* without any known hemoglobin disorders, such as sickle cell disease, sickle cell trait, β-thalassemia, etc.
Around 30 participants each (in Canada):
* with the homozygous form of sickle cell disease (HbSS)
* with the heterozygous form of sickle cell disease (HbAS)
* without any known hemoglobin disorders, such as sickle cell disease, sickle cell trait, β-thalassemia, etc. Receives: Diagnostic Test: High performance liquid chromatography; Device: Automated sickling test; Diagnostic Test: HbS solubility test; Device: HemoTypeSC; Device: Sickle SCAN; Device: Gazelle Hb Variant Test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity, Specificity, Positive Predictive Value and Negative Predictive Value
The following metrics will be determined for the low-cost tests to be evaluated as indicated below (where TP = true positive, TN = true negative, FP = false positive, FN = false negative):
- Sensitivity = TP/(TP + FN)
- Specificity = TN/(FP + TN)
- Positive predictive value = TP/(TP + FP)
- Negative predictive value = TN/(TN + FN)
These metrics will be calculated for the low-cost technologies against the reference test, HPLC, for detecting the presence of sickle hemoglobin and β- thalassemia. The low-cost technologies include automated sickling test (standard sickling test enhanced using low-cost microscopy and machine learning), solubility test, HemoTypeSC, Sickle SCAN, and Gazelle Hb Variant test. The test results of the low-cost technologies will be compared with those of the reference test to get the values of TP, TN, FP and FN, which will then be used to calculate the metrics listed above.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2022
- Study start20 Sep 2022
- Primary completion30 Mar 2023
- Study completion30 Mar 2023
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 Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Around 90 participants will be recruited in Canada - 30 with SCD (HbSS), 30 with SCT (HbAS), and 30 healthy participants (HbAA). Around 120 participants will be recruited in Nepal - 20 with SCD (HbSS), 20 with SCT (HbAS), 20 with sickle cell / β-thalassaemia compound heterozygous form (HbS/β-thalassemia), 20 with β-thalassaemia (Hbβ/ β-thalassemia), 20 with β-thalassaemia trait or carrier form (HbA/β-thalassemia), and 20 healthy participants (HbAA). 3-4 mL of blood will be drawn using standard phlebotomy practices. The following tests will be performed: a. Low-cost tests i. Sickling test with low-cost microscope and automated screening with machine learning ii. Sickling test with traditional microscope (conventional manual screening used in Nepal) iii. HbS solubility test iv. Commercial point-of-care assays (HemoTypeSC and Sickle SCAN) v. Gazelle Hb variant test b. Gold standard test: HPLC, for determining the accuracies of low-cost screening techniques
- Masking
- None (open label)
- Enrolment
- 145 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Boris Stoeber, University of British Columbia
- Investigators
- Boris Stoeber, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05506358
- Sponsor's protocol ID
- H22-00294
- Other IDs
- 85/2022, H22-00294, H21-01929
- Status last verified
- May 2024
- First submitted
- 15 Aug 2022
- Last updated
- 4 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Only de-identified data and test results will be shared. The test results for the low-cost tests and HPLC tests will be published in aggregate form. De-identified images of blood films will be deposited in an online public repository, such as Federated Research Data Repository (FRDR).
Publications
Shrestha P, Lohse H, Bhatla C, McCartney H, Alzaki A, Sandhu N, Oli PK, Chaudhary S, Amid A, Onell R, Au N, Merkeley H, Kapoor V, Pande R, Stoeber B. Evaluation of low-cost techniques to detect sickle cell disease and beta-thalassemia: an open-label, international, multicentre study. Lancet Reg Health Southeast Asia. 2025 Mar 29;35:100571. doi: 10.1016/j.lansea.2025.100571. eCollection 2025 Apr.
PubMed 40230447