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Hemoglobin Desaturation in Sickle Cell Disease

19 maggio 2022 aggiornato da: Lalitha Nayak, University Hospitals Cleveland Medical Center

Hemoglobin Desaturation and RBC Adhesion: Potential Therapeutic Targets in Sickle Cell Disease

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.

Panoramica dello studio

Stato

Completato

Condizioni

Descrizione dettagliata

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.

Tipo di studio

Osservativo

Iscrizione (Effettivo)

1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • Ohio
      • Cleveland, Ohio, Stati Uniti, 44106
        • University Hospitals Cleveland Medical Center

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Metodo di campionamento

Campione non probabilistico

Popolazione di studio

Individuals with HbSS Sickle Cell Disease

Descrizione

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. -

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Evaluation for resting hypoxia
Lasso di tempo: Through study completion, up to approximately 4 years
We will test resting SpO2 and night-time oxymetry to obtain Hb saturation results.
Through study completion, up to approximately 4 years
Evaluation for exertional hypoxia
Lasso di tempo: Through study completion, up to approximately 4 years
We will evaluate 6MWT results and obtain Hb saturation results.
Through study completion, up to approximately 4 years
Evaluation of hypoxia and its effect on CBC
Lasso di tempo: Through study completion, up to approximately 4 years
CBC results will be evaluated
Through study completion, up to approximately 4 years
Evaluation of hypoxia and its effect on reticulocyte count
Lasso di tempo: Through study completion, up to approximately 4 years
Reticulocyte count will be evaluated
Through study completion, up to approximately 4 years
Evaluation of hypoxia and its effect on LDH
Lasso di tempo: Through study completion, up to approximately 4 years
LDH level will be evaluated
Through study completion, up to approximately 4 years
Evaluation of hypoxia and its effect on serum chemistry
Lasso di tempo: Through study completion, up to approximately 4 years
Serum chemistry through a comprehensive panel will be evaluated
Through study completion, up to approximately 4 years
Evaluation of patient's incidence of hypoxia-related symptoms
Lasso di tempo: 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.
Through study completion, up to approximately 4 years
Evaluation of hypoxia and its effect on echocardiogram results
Lasso di tempo: Through study completion, up to approximately 4 years
Screening echocardiogram
Through study completion, up to approximately 4 years
Evaluation of patient's incidence of hypoxia-related nocturnal symptoms
Lasso di tempo: 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.
Through study completion, up to approximately 4 years
Examination of amount of baseline RBC adhesion and HEA in vitro in adults with HbSS
Lasso di tempo: 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
Through study completion, up to approximately 4 years
Examination of baseline FACS results in adults with HbSS
Lasso di tempo: 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.
Through study completion, up to approximately 4 years
Examination of amount of baseline RBC adhesion and HEA in vitro in adults with HbSS
Lasso di tempo: 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
Through study completion, up to approximately 4 years
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.
Lasso di tempo: 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
2 months
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
Lasso di tempo: 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
2 months
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.
Lasso di tempo: 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
2 months
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
Lasso di tempo: 2 months
We will repeat Hb saturation testing
2 months
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.
Lasso di tempo: 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
2 months
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
Lasso di tempo: 2 months
Amount of WBC activation will be determined
2 months
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.
Lasso di tempo: 2 months
CBC results will be examined for any suggestive changes
2 months
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.
Lasso di tempo: 2 months
Reticulocyte count will be examined for any suggestive changes
2 months
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.
Lasso di tempo: 2 months
LDH level will be examined for any suggestive changes
2 months
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.
Lasso di tempo: 2 months
Serum chemistry through a comprehensive panel will be examined for any suggestive changes
2 months

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

University Hospitals Cleveland Medical Center

Investigatori

  • Investigatore principale: Jane Little, MD, University Hospitals Cleveland Medical Center

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

23 marzo 2018

Completamento primario (Effettivo)

1 febbraio 2022

Completamento dello studio (Effettivo)

1 febbraio 2022

Date di iscrizione allo studio

Primo inviato

21 marzo 2019

Primo inviato che soddisfa i criteri di controllo qualità

5 aprile 2019

Primo Inserito (Effettivo)

9 aprile 2019

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

26 maggio 2022

Ultimo aggiornamento inviato che soddisfa i criteri QC

19 maggio 2022

Ultimo verificato

1 maggio 2022

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 03-18-23

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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