Evaluation of Low-cost Techniques for Detecting Sickle Cell Disease and β-thalassemia in Nepal and Canada

NCT05506358 | Completed Results FDA Device

• 3 other identifiers: H22-0029485/2022H21-01929
• Study Type: interventional
• Target: 145
• Locations: 2 countries
• Sites: 3

Brief 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%). 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:

1. 1.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
2. 2.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
3. 3.Gazelle diagnostic device can detect β-thalassaemia and SCD/SCT with an overall accuracy greater than 90%, compared with HPLC as the reference test

Conditions

Sickle Cell Disease; Sickle Cell Trait; Beta-Thalassemia; Sickle Cell-Beta Thalassemia; Sickle Cell-SS Disease

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

Outcome Measures

Primary Outcomes (1)

• 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.

  baseline

Study Arms (1)

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.

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

Interventions

High performance liquid chromatography DIAGNOSTIC_TEST

High performance liquid chromatography (HPLC) using the D10 System by Bio-Rad Laboratories will be used as the gold standard test.

1) HbSS; 2) HbAS; 3) HbS/β-thalassemia; 4)Hbβ/β-thalassemia; 5) HbA/β- thalassemia; 6) HbAA

Automated sickling test DEVICE

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.

1) HbSS; 2) HbAS; 3) HbS/β-thalassemia; 4)Hbβ/β-thalassemia; 5) HbA/β- thalassemia; 6) HbAA

HbS solubility test DIAGNOSTIC_TEST

Standard HbS solubility test currently used in Nepal (e.g. Sicklevue) will be used as one of the low-cost tests

1) HbSS; 2) HbAS; 3) HbS/β-thalassemia; 4)Hbβ/β-thalassemia; 5) HbA/β- thalassemia; 6) HbAA

HemoTypeSC DEVICE

A point-of-care lateral flow assay, HemoTypeSC (https://www.hemotype.com/), will be used as one of the low-cost tests

1) HbSS; 2) HbAS; 3) HbS/β-thalassemia; 4)Hbβ/β-thalassemia; 5) HbA/β- thalassemia; 6) HbAA

Sickle SCAN DEVICE

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

1) HbSS; 2) HbAS; 3) HbS/β-thalassemia; 4)Hbβ/β-thalassemia; 5) HbA/β- thalassemia; 6) HbAA

Gazelle Hb Variant Test DEVICE

A portable electrophoresis machine, Gazelle diagnostic device (https://hemexhealth.com/), will be used as one of the low-cost tests

1) HbSS; 2) HbAS; 3) HbS/β-thalassemia; 4)Hbβ/β-thalassemia; 5) HbA/β- thalassemia; 6) HbAA

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• individuals with SCD (HbSS)
• individuals with SCT (HbAS)
• individuals with sickle cell/β-thalassemia compound heterozygous form (HbS/β-thalassemia)
• individuals with β-thalassemia (Hbβ/β-thalassemia)
• individuals with β-thalassemia trait or carrier form (HbA/β- thalassemia)
• 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:
• individuals with SCD (HbSS)
• individuals with SCT (HbAS)
• 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.

You may not qualify if:

• Transfusion within the last 3 months
• Pregnancy Participants who wish to withdraw from the study will also be excluded.

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (3)

BC Children's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Mount Sagarmatha Polyclinic and Diagnostic Center

Nepalgunj, Banke, Nepal

Location

Related Publications (1)

• 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.

  PMID: 40230447 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Sickle Cell Trait; beta-Thalassemia

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Thalassemia

Results Point of Contact

• Title: Pranav Shrestha
• Organization: The University of British Columbia

pranav.shrestha@alumni.ubc.ca

6507893270

Study Officials

• Boris Stoeber

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: All the participants and study team members will be informed of the tests and devices used in the study.
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in the Department of Electrical and Computer Engineering and in the Department of Mechanical Engineering

Model Details: 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

Study Record Dates

• First Submitted: August 15, 2022
• First Posted: August 18, 2022
• Study Start: September 20, 2022
• Primary Completion: March 30, 2023
• Study Completion: March 30, 2023
• Last Updated: June 4, 2024
• Results First Posted: June 4, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

NE (1); CA (2)