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Hemoglobin Desaturation in Sickle Cell Disease

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ClinicalTrials.gov Identifier: NCT03908385
Recruitment Status : Recruiting
First Posted : April 9, 2019
Last Update Posted : April 9, 2019
Sponsor:
Information provided by (Responsible Party):
Jane Little, University Hospitals Cleveland Medical Center

Brief Summary:
As part of routine care for SCD, some people are found to have low oxygen levels (≤ 88%) while sleeping, at rest, or with exercise. Testing is done with a small portable device positioned on the finger that measures oxygen levels during sleep, at rest, or following exercise. The investigators start oxygen treatment for people with low levels of oxygen. As a part of this study, the investigators will find out if any changes in cell "stickiness" occur with low oxygen levels (at rest, at night, or with exertion) and if cells become "less sticky" with oxygen treatment. Study subjects will be seen before testing and 2 months after testing. In some cases (people with low oxygen levels during testing), study subjects will have been prescribed oxygen, and the investigators will test the effects of that treatment on the stickiness of red cells.

Condition or disease
Sickle Cell Disease

Detailed Description:

In SCD, exertional hypoxia and nocturnal hemoglobin desaturation (NHD, or hemoglobin deoxygenation during sleep) are common, treatable, and associated with bad outcomes in children and young adults15,16. The median life-expectancy of SCD has risen dramatically in the last 40 years. One consequence of this is an expanding young adult population in whom the comorbidities are not yet fully characterized. The prevalence, clinical consequences, and treatment outcomes of exertional hypoxia and NHD are poorly described in adults with SCD. Therefore, it is important to identify and better understand any clinically significant hypoxia (during exercise or sleep or at rest) in this expanding adult population. The investigators will study whether RBC adhesion at baseline and when exposed to hypoxia in vitro is significantly increased in adult HbSS patients with baseline hypoxia, exertional hypoxia or nocturnal NHD due to RBC membrane changes arising from prolonged in vivo exposure to hypoxia, which may be mitigated by oxygen therapy.

Hypotheses: The investigators hypothesize that disease activity and RBC adhesion (under normoxia) will be greater in subjects with HbSS plus baseline in vivo hypoxia, exertional hypoxia, or NHD, due to RBC membrane damage from prolonged hypoxia in vivo. Successful treatment with therapeutic oxygen, at baseline, with exertion, or during sleep, may decrease RBC adhesion in vitro.

Specific Aim 1: To evaluate for resting hypoxia, exertional hypoxia or NHD, and its clinical associations, in adults with HbSS.

Specific Aim 2: To examine baseline RBC adhesion under normoxia or hypoxia in vitro in adults with HbSS, with and without in vivo resting or exertional hypoxia or NHD.

Specific Aim 3: To examine serial changes in S-RBC adhesion at baseline and with hypoxia in vitro, in adults with HbSS and resting or exertional hypoxia or NHD, before and after therapeutic intervention with oxygen.

The investigators are testing whether:

  1. Subjects with Hb desaturation at baseline, with exertion, or during sleep (NHD), compared to those without, will have increased disease activity (exertional or nocturnal symptoms, priapism, WBC activation, reticulocytosis, and/or hemolysis).
  2. S-RBCs from subjects with clinical Hb desaturation at rest, with exertion, or during sleep, compared to those without, will have increased adhesion at baseline and when exposed to hypoxia in vitro.

2.A. Treatment of baseline hypoxia, exertional hypoxia, and/or NHD with supplemental oxygen will decrease S-RBC adhesion and HEA, and may decrease symptoms, especially night- time symptoms.


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Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Hemoglobin Desaturation and RBC Adhesion: Potential Therapeutic Targets in Sickle Cell Disease
Actual Study Start Date : March 23, 2018
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine





Primary Outcome Measures :
  1. Evaluation for resting hypoxia [ Time Frame: Through study completion, up to approximately 4 years ]
    We will test resting SpO2 and night-time oxymetry to obtain Hb saturation results.

  2. Evaluation for exertional hypoxia [ Time Frame: Through study completion, up to approximately 4 years ]
    We will evaluate 6MWT results and obtain Hb saturation results.

  3. Evaluation of hypoxia and its effect on CBC [ Time Frame: Through study completion, up to approximately 4 years ]
    CBC results will be evaluated

  4. Evaluation of hypoxia and its effect on reticulocyte count [ Time Frame: Through study completion, up to approximately 4 years ]
    Reticulocyte count will be evaluated

  5. Evaluation of hypoxia and its effect on LDH [ Time Frame: Through study completion, up to approximately 4 years ]
    LDH level will be evaluated

  6. Evaluation of hypoxia and its effect on serum chemistry [ Time Frame: Through study completion, up to approximately 4 years ]
    Serum chemistry through a comprehensive panel will be evaluated

  7. Evaluation of patient's incidence of hypoxia-related symptoms [ Time Frame: Through study completion, up to approximately 4 years ]
    Incidence of hypoxia-related symptoms will be obtained from review of the patient's chart and approved symptom questionnaire.

  8. Evaluation of hypoxia and its effect on echocardiogram results [ Time Frame: Through study completion, up to approximately 4 years ]
    Screening echocardiogram

  9. Evaluation of patient's incidence of hypoxia-related nocturnal symptoms [ Time Frame: Through study completion, up to approximately 4 years ]
    Incidence of nocturnal hypoxia-related symptoms will be obtained from review of the patient's chart and approved symptom questionnaire.

  10. Examination of amount of baseline RBC adhesion and HEA in vitro in adults with HbSS [ Time Frame: Through study completion, up to approximately 4 years ]
    Amount of S-RBC adhesion to LN on the SCD and Hypoxia Biochips will be quantitated, using <400 μL surplus whole blood in EDTA, obtained during routine clinical care (as published previously1,6-8), at the clinic visit immediately prior to night-time oximetry and 6MWT

  11. Examination of baseline FACS results in adults with HbSS [ Time Frame: Through study completion, up to approximately 4 years ]
    Fluorescent Activated Cell Sorting (FACS) following incubation with antibodies to CD14, CD16, and CX3CR1 will be performed on 3-400 μL of surplus whole blood.

  12. Examination of amount of baseline RBC adhesion and HEA in vitro in adults with HbSS [ Time Frame: Through study completion, up to approximately 4 years ]
    Simple t-tests will be used to compare RBC adhesion, HEA to LN and monocyte activation in patients with clinically significant hypoxia and those without any hypoxia

  13. Examination of serial changes in incidence of nocturnal symptoms at baseline and with hypoxia, in adults with HbSS and resting or exertional hypoxia or NHD, before and after therapeutic intervention with oxygen. [ Time Frame: 2 months ]
    At ~2 months after initial testing (and >6 weeks on treatment, if needed), all subjects will be re-evaluated for incidence of hypoxia-related nocturnal symptoms through review of the patient's chart and approved symptom questionnaire

  14. Examination of serial changes in amount of S-RBC adhesion at baseline and with hypoxia in vitro, in adults with HbSS and resting or exertional hypoxia or NHD, before and after therapeutic intervention with oxygen [ Time Frame: 2 months ]
    At ~2 months after initial testing (and >6 weeks on treatment, if needed), all subjects will be re-evaluated for amount of RBC adhesion

  15. Examination of serial changes in incidence of hypoxia-related symptoms at baseline and with hypoxia, in adults with HbSS and resting or exertional hypoxia or NHD, before and after therapeutic intervention with oxygen. [ Time Frame: 2 months ]
    At ~2 months after initial testing (and >6 weeks on treatment, if needed), all subjects will have incidence of hypoxia-related symptoms re-evaluated through review of the patient's chart and approved symptom questionnaire

  16. Examination of serial changes in Hb saturation at baseline and with hypoxia in vitro, in adults with HbSS and resting or exertional hypoxia or NHD, before and after therapeutic intervention with oxygen [ Time Frame: 2 months ]
    We will repeat Hb saturation testing

  17. Examination of serial changes in amount of S-RBC adhesion at baseline and with hypoxia in vitro, in adults with HbSS and resting or exertional hypoxia or NHD, before and after therapeutic intervention with oxygen. [ Time Frame: 2 months ]
    Paired t-test on S-RBC adhesion to LN and HEA before and after oxygen therapy, in subjects with and without clinically significant hypoxia will be performed

  18. Examination of serial changes in amount of WBC activation at baseline and with hypoxia in vitro, in adults with HbSS and resting or exertional hypoxia or NHD, before and after therapeutic intervention with oxygen [ Time Frame: 2 months ]
    Amount of WBC activation will be determined

  19. Examination of serial changes in CBC at baseline and with hypoxia in vitro, in adults with HbSS and resting or exertional hypoxia or NHD, before and after therapeutic intervention with oxygen. [ Time Frame: 2 months ]
    CBC results will be examined for any suggestive changes

  20. Examination of serial changes in reticulocyte count at baseline and with hypoxia in vitro, in adults with HbSS and resting or exertional hypoxia or NHD, before and after therapeutic intervention with oxygen. [ Time Frame: 2 months ]
    Reticulocyte count will be examined for any suggestive changes

  21. Examination of serial changes in LDH at baseline and with hypoxia in vitro, in adults with HbSS and resting or exertional hypoxia or NHD, before and after therapeutic intervention with oxygen. [ Time Frame: 2 months ]
    LDH level will be examined for any suggestive changes

  22. Examination of serial changes in serum chemistry at baseline and with hypoxia in vitro, in adults with HbSS and resting or exertional hypoxia or NHD, before and after therapeutic intervention with oxygen. [ Time Frame: 2 months ]
    Serum chemistry through a comprehensive panel will be examined for any suggestive changes


Biospecimen Retention:   None Retained
Blood samples


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Individuals with HbSS Sickle Cell Disease
Criteria

Inclusion Criteria:

  1. Male or Female > 18 year of age at the time of consent.
  2. Documentation of Sickle Cell Disease, phenotypically HbSS (including S-Beta 0 thalassemia)
  3. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
  4. English speaking patient

Exclusion Criteria:

  1. Ongoing Oxygen therapy.
  2. active pregnancy, due to complex pathophysiology during that interval.
  3. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data. -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03908385


Contacts
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Contact: Jane Little, MD 216-844-1652 Jane.Little@UHhospitals.org

Locations
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United States, Ohio
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Jane Little, MD         
Sponsors and Collaborators
University Hospitals Cleveland Medical Center
Investigators
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Principal Investigator: Jane Little, MD University Hospitals Cleveland Medical Center
  Study Documents (Full-Text)

Documents provided by Jane Little, University Hospitals Cleveland Medical Center:
Study Protocol  [PDF] March 23, 2018


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Responsible Party: Jane Little, Director, Adult Sickle Cell provider, University Hospitals Cleveland Medical Center
ClinicalTrials.gov Identifier: NCT03908385     History of Changes
Other Study ID Numbers: 03-18-23
First Posted: April 9, 2019    Key Record Dates
Last Update Posted: April 9, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn