Clinical trial NCT03908385: Hemoglobin Desaturation in Sickle Cell Disease
Official title: Hemoglobin Desaturation and RBC Adhesion: Potential Therapeutic Targets in Sickle Cell Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sickle Cell Disease
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
First posted: 2019-04-09
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with HbSS Sickle Cell Disease

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.

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.

Eligibility 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. -

Primary outcomes:
measure: Evaluation for resting hypoxia
timeFrame: Through study completion, up to approximately 4 years
measure: Evaluation for exertional hypoxia
timeFrame: Through study completion, up to approximately 4 years
measure: Evaluation of hypoxia and its effect on CBC
timeFrame: Through study completion, up to approximately 4 years
measure: Evaluation of hypoxia and its effect on reticulocyte count
timeFrame: Through study completion, up to approximately 4 years
measure: Evaluation of hypoxia and its effect on LDH
timeFrame: Through study completion, up to approximately 4 years
measure: Evaluation of hypoxia and its effect on serum chemistry
timeFrame: Through study completion, up to approximately 4 years
measure: Evaluation of patient's incidence of hypoxia-related symptoms
timeFrame: Through study completion, up to approximately 4 years
measure: Evaluation of hypoxia and its effect on echocardiogram results
timeFrame: Through study completion, up to approximately 4 years
measure: Evaluation of patient's incidence of hypoxia-related nocturnal symptoms
timeFrame: Through study completion, up to approximately 4 years
measure: Examination of amount of baseline RBC adhesion and HEA in vitro in adults with HbSS
timeFrame: Through study completion, up to approximately 4 years
measure: Examination of baseline FACS results in adults with HbSS
timeFrame: Through study completion, up to approximately 4 years
measure: Examination of amount of baseline RBC adhesion and HEA in vitro in adults with HbSS
timeFrame: Through study completion, up to approximately 4 years
measure: 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.
timeFrame: 2 months
measure: 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
timeFrame: 2 months
measure: 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.
timeFrame: 2 months
measure: 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
timeFrame: 2 months
measure: 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.
timeFrame: 2 months
measure: 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
timeFrame: 2 months
measure: 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.
timeFrame: 2 months
measure: 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.
timeFrame: 2 months
measure: 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.
timeFrame: 2 months
measure: 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.
timeFrame: 2 months
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center
name: Jane Little, MD
role: PRINCIPAL_INVESTIGATOR
References: