Genotype -Phenotype Correlation of PKLR Variants With Pyruvate Kinase, 2,3-Diphosphglycerate and Adenosine Triphosphate Activities in Red Blood Cells of People With Sickle Cell Disease

NCT03685721 | Recruiting

• 2 other identifiers: 18014618-H-0146
• Study Type: observational
• Target: 800
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Some people with the same disorder on a genetic level have more complications than others. Researchers want to look for a link between the PKLR gene and sickle cell disease (SCD) symptoms. The PKLR gene helps create a protein, called pyruvate kinase that is essential in normal functioning of the red blood cell. Differences in the PKLR gene, called genetic variants, may cause some changes in the pyruvate kinase protein and other proteins, that can affect functioning of the red blood cell adding to the effect of SCD. Researchers can study these differences by looking at DNA (the material that determines inherited characteristics). Objective: To study how the PKLR gene affects sickle cell disease. Eligibility: Adults ages 18-80 of African descent. They may have sickle cell disease or not. They must not have had a transfusion recently or have a known deficiency of pyruvate kinase. They cannot be pregnant. Design: Participants will be screened with questions. Participants will have blood drawn by needle in an arm vein. The blood will be genetically tested. Not much is known about how genes affect SCD, so the test results will not be shared with participants or their doctors. ...

Conditions

Sickle Cell; PKLR Variants; Adenosine Triphosphate Activities

Keywords

ATP; Trait; GDP; Genetics; Natural History

Outcome Measures

Primary Outcomes (3)

• Genotype the 4 PKLR intron-2 variants

  To have genotyped the 4 PKLR intron-2 variants in SCD patients from the NHLBI cohort using genomic DNA and compare them to a cohort of healthy ethnic-matched non-SCD controls and a cohort of sickle cell trait carriers, with those reported in 1000 genome project (http://www.1000genomes.org).

  Upon enrollment of each subject

• Analysis of PK-R transcriptome in red blood cells

  Have a correlated profile of the PK-R RNA sequence with the 4 PKLR intronic genetic variants.

  Interim analysis performed for each group N=125

• Correlation of 2,3-DPG, ATP and pyruvate kinase activities with PKLR intron-2 variants

  Assess correlation between the quantitative assays and genotype

  Interim analysis performed for each group N=125

Study Arms (3)

HbAS

HbAS genotype, of African American descent;Between 18 and 80 years of age

Healthy control

African American descent;Between 18 and 80 years of age

SCD

HbSS, HbSC, HbSbeta-thal has sickle cell disease and is of African American descent;Between 18 and 80 years of age

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study will be listed on the clinicaltrials.gov, Clinical Center research studies, and the National Heart, Lung and Blood Institute patient recruitment websites. Patients who are followed on other NHLBI sickle cell protocols may be asked to participate in this study, particularly subjects enrolled in the Natural History of Sickle Cell Disease (NCT00081523; 04-H-0161).

You may not qualify if:

• Self-reported history of blood transfusion within the last 8 weeks
• Known to have pyruvate kinase deficiency and be on AG348
• All volunteers will undergo the consent process under this protocol to allow for eligibility assessment. Once they have been consented to participate, they will undergo procedures per Protocol.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

Study Officials

• Swee Lay Thein, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dianna S Lovins

CONTACT

(301) 480-3765; dianna.lovins@nih.gov

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: September 26, 2018
• Study Start: October 11, 2018
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03-06

Locations

US (1)