An interventional study of High performance liquid chromatography and Automated sickling test in Sickle Cell Disease, Sickle Cell Trait and Beta-Thalassemia, sponsored by University of British Columbia. Completed at 3 sites in 2 countries. Open to participants aged 1 Year and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-06-04.
Sponsored by University of British Columbia · Not applicable, Interventional, and Diagnostic
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.
The investigators hypothesize that:
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:
Long-term objectives of the overall project are to:
The plan of the study to screen the communities (e.g. in Nepalgunj, in Vancouver) using the following:
a. 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.
43 studies on the registry are indexed under Sickle Cell Trait; 11 are open to participants now.
This study's enrollment of 145 is above the median of 63 across 22 interventional studies indexed under Sickle Cell Trait.
Browse Sickle Cell Trait studies →University of British Columbia is the lead sponsor of 1,339 studies on the registry; 259 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 1 (17%) have results posted.
Compared within Sickle Cell Trait, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Anemia, Sickle Cell. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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:
The following number of participants will be included in Canada:
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.
Exclusion Criteria:
The exclusion criteria for the study:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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
High performance liquid chromatography (HPLC) using the D10 System by Bio-Rad Laboratories will be used as the gold standard test.
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.
Standard HbS solubility test currently used in Nepal (e.g. Sicklevue) will be used as one of the low-cost tests
A point-of-care lateral flow assay, HemoTypeSC (https://www.hemotype.com/), will be used as one of the low-cost tests
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
A portable electrophoresis machine, Gazelle diagnostic device (https://hemexhealth.com/), will be used as one of the low-cost tests
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): 1. Sensitivity = TP/(TP + FN) 2. Specificity = TN/(FP + TN) 3. Positive predictive value = TP/(TP + FP) 4. 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.
Time frame: baseline
| Milestone | HbSS | HbAS | HbS/β-thalassemia | HbA/β-thalassemia | HbAA |
|---|---|---|---|---|---|
| Started | 33 | 45 | 11 | 26 | 30 |
| Completed | 29 | 45 | 11 | 23 | 30 |
| Not completed | 4 | 0 | 0 | 3 | 0 |
| Withdrew: Sickle cell disease with transfusion within 3 months | 2 | 0 | 0 | 0 | 0 |
| Withdrew: Sickle cell disease with hereditary persistence of fetal hemoglobin (hpfh) | 2 | 0 | 0 | 0 | 0 |
| Withdrew: Beta-thalassemia major with transfusion within 2 months | 0 | 0 | 0 | 1 | 0 |
| Withdrew: Sample hemolysis observed under the microscope | 0 | 0 | 0 | 1 | 0 |
| Withdrew: Hbe trait | 0 | 0 | 0 | 1 | 0 |
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): 1. Sensitivity = TP/(TP + FN) 2. Specificity = TN/(FP + TN) 3. Positive predictive value = TP/(TP + FP) 4. 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.
| percentage | HbSS | HbAS | HbS/β-thalassemia | HbA/β-thalassemia | HbAA |
|---|---|---|---|---|---|
| Gazelle (sensitivity) | 96.6 | 100 | 0 | 91.3 | 96.7 |
| Gazelle (specificity) | 89.9 | 100 | 99.2 | 99.1 | 98.1 |
| Gazelle (PPV) | 71.8 | 100 | 0 | 95.5 | 93.5 |
| Gazelle (NPV) | 99 | 100 | 92 | 98.3 | 99.1 |
| HemoTypeSC (sensitivity) | 100 | 97.8 | 0 | 0 | 100 |
| HemoTypeSC (specificity) | 89 | 100 | 100 | 100 | 78.7 |
| HemoTypeSC (NPV) | 100 | 98.9 | 92 | 83.3 | 100 |
| Sickle SCAN (sensitivity) | 100 | 100 | 0 | 0 | 100 |
| Sickle SCAN (specificity) | 89.9 | 100 | 100 | 100 | 78.7 |
| Sickle SCAN (NPV) | 100 | 100 | 92 | 83.3 | 100 |
Collected over 1 day. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| HbSS | 0/29 (0%) | 0/29 (0%) | 0/29 (0%) |
| HbAS | 0/45 (0%) | 0/45 (0%) | 0/45 (0%) |
| HbS/β-thalassemia | 0/11 (0%) | 0/11 (0%) | 0/11 (0%) |
| HbA/β-thalassemia | 0/23 (0%) | 0/23 (0%) | 0/23 (0%) |
| HbAA | 0/30 (0%) | 0/30 (0%) | 0/30 (0%) |
Note that the demographic information (age, sex) is reported for all different groups combined, and individual analysis of age and sex distribution per group is not performed due to the way the data was collected. In Canada, only averages and ranges for age and sex were collected rather than distribution per group.
| Age, Categorical(Participants) | 1) HbSS; 2) HbAS; 3) HbS/β-thalassemia; 4) HbA/β-thalassemia; 5) HbAA |
|---|---|
| <=18 years | 33 |
| Between 18 and 65 years | 103 |
| >=65 years | 2 |
| Sex: Female, Male(Participants) | 1) HbSS; 2) HbAS; 3) HbS/β-thalassemia; 4) HbA/β-thalassemia; 5) HbAA |
|---|---|
| Female | 81 |
| Male | 57 |
| Race and Ethnicity Not Collected(Participants) | 1) HbSS; 2) HbAS; 3) HbS/β-thalassemia; 4) HbA/β-thalassemia; 5) HbAA |
|---|
| Region of Enrollment(participants) | 1) HbSS; 2) HbAS; 3) HbS/β-thalassemia; 4) HbA/β-thalassemia; 5) HbAA |
|---|---|
| Canada | 27 |
| Nepal | 111 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: 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).
Ran from Sep 2022 to primary completion in Mar 2023, 6 months.
Results were first posted in Jun 2024, 1 year 2 months after primary completion.
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