- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02692872
Screening for Alpha Thalassemia in Healthy Volunteers
Screening for Alpha Globin Deletions
Background:
Alpha thalassemia is a blood disorder. It is caused by genetic deletions. Part of the DNA is missing from a group of genes called alpha globin. Alpha thalassemias are some of the most common genetic deletions. We are testing for alpha thalassemia trait. Alpha thalassemia trait is when someone has only two out of the normal four alpha globin genes. In some people, they lead to no symptoms. Others have changes that lead to disease, including mild anemia. Researchers want to learn more about alpha thalassemia and blood vessels. This may allow them to develop new treatments for blood diseases such as sickle cell disease.
Objective:
To better understand how alpha globin deletions in healthy people affect blood vessels.
Eligibility:
Healthy volunteers ages 18-39 who self-report African ancestry.
Design:
Participants will provide a one-time saliva sample. This can be by mail, in-person at a study event, or at NIH.
Participants will get a small kit to collect their saliva sample. The kit has easy instructions. The sample does not need to be put in the refrigerator.
Participants will spit a small amount of saliva (less than half a teaspoon) into a collection tube.
Participants will close the funnel lid tightly, and then unscrew the funnel lid from the tube. They will then close the tube tightly with the small cap provided and shake the tube for 5 seconds.
Participants will place the tube in the provided envelope and mail it to NIH. The specimen will be stored and processed in the lab.
Participants may be invited to participate in more research studies, whether or not researchers find that they have alpha thalassemia trait.
Study Overview
Status
Conditions
Detailed Description
Many of the complications of sickle cell disease, such as stroke, kidney damage, skin ulceration,pulmonary hypertension, and cardiac hypertrophy are prevented, delayed or reduced by inheritance of one of more deletions of the alpha globin genes. Our long-term research goal is to understand how deletions of alpha globin protect against the vascular complications of sickle cell disease.
Deletions of alpha globin are common and found in approximately 5% of the world s population.They are especially common among Africans and people of African ancestry, as well as in India, China, and the Pacific Islands, where prevalence can range from 5 - 80%. A single deletion has little effect on the red blood cell, but two deletions can give rise to alpha thalassemia, a mild microcytic anemia. Patients with sickle cell disease who have two alpha globin deletions tend to have a higher hemoglobin level, smaller red blood cells, and a lower fraction of circulating reticulocytes - consistent with decreased hemolysis and red cell turnover. They also have a lower number of dense or irreversibly sickled cells. These changes might explain why alpha globin deletions reduce the severity of sickle cell disease.
However, a novel function for alpha globin as a regulator of endothelial nitric oxide (NO) has recently been identified that raises new questions about how alpha globin deletions protect against sickle cell disease. We hypothesize that individuals with two alpha globin deletions will have decreased gene expression and protein levels of alpha globin in vascular endothelium, permitting more NO to diffuse across the myoendothelial junction, compared to individuals who have all four alpha globin genes intact. In this protocol we will screen healthy volunteers to identify those with two alpha globin deletions; these individuals as well as matched controls will be referred to a separate protocol to undergo studies of vascular endothelial function.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Amy P Ruhl, M.D.
- Phone Number: (240) 669-5776
- Email: parker.ruhl@nih.gov
Study Contact Backup
- Name: Mary J Jackson, R.N.
- Phone Number: (301) 761-5667
- Email: alpha.study@nih.gov
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20892
- Recruiting
- National Institutes of Health Clinical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
- INCLUSION CRITERIA:
Subject report of the following:
- Age 18 - 39
- Self-report of African ancestry
- Willingness and legal ability to give and sign informed study consent
EXCLUSION CRITERIA:
There are no exclusion criteria for this screening protocol
Study Plan
How is the study designed?
Design Details
- Observational Models: Other
- Time Perspectives: Other
Cohorts and Interventions
Group / Cohort |
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1
We plan to perform genetic screening of up to 2,000 individuals of African ancestry, an ethnic group with a high prevalence of alpha thalassemia.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Identify Presence of Double Alpha Globin Deletions in Healthy Volunteers.
Time Frame: Ongoing
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As this is not a treatment protocol, there is no primary endpoint.
The primary objective is to identify presence of double alpha globin deletions in healthy volunteers.
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Ongoing
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Collaborators and Investigators
Investigators
- Principal Investigator: Amy P Ruhl, M.D., National Institute of Allergy and Infectious Diseases (NIAID)
Publications and helpful links
General Publications
- Embury SH, Dozy AM, Miller J, Davis JR Jr, Kleman KM, Preisler H, Vichinsky E, Lande WN, Lubin BH, Kan YW, Mentzer WC. Concurrent sickle-cell anemia and alpha-thalassemia: effect on severity of anemia. N Engl J Med. 1982 Feb 4;306(5):270-4. doi: 10.1056/NEJM198202043060504.
- Piel FB, Weatherall DJ. The alpha-thalassemias. N Engl J Med. 2014 Nov 13;371(20):1908-16. doi: 10.1056/NEJMra1404415.
- Straub AC, Lohman AW, Billaud M, Johnstone SR, Dwyer ST, Lee MY, Bortz PS, Best AK, Columbus L, Gaston B, Isakson BE. Endothelial cell expression of haemoglobin alpha regulates nitric oxide signalling. Nature. 2012 Nov 15;491(7424):473-7. doi: 10.1038/nature11626. Epub 2012 Oct 31.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 160065
- 16-I-0065
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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