Study of Ocular Blood Flow in Patients With Glaucoma and/or Obstructive Sleep Apnea Syndrome (OSAS)
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|ClinicalTrials.gov Identifier: NCT00874913|
Recruitment Status : Unknown
Verified October 2012 by University Hospital, Grenoble.
Recruitment status was: Recruiting
First Posted : April 3, 2009
Last Update Posted : October 10, 2012
|First Submitted Date ICMJE||April 2, 2009|
|First Posted Date ICMJE||April 3, 2009|
|Last Update Posted Date||October 10, 2012|
|Start Date ICMJE||September 2006|
|Estimated Primary Completion Date||January 2014 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||ocular blood flow [ Time Frame: 9 months ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT00874913 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||comparisons between OSAS patients and healthy controls [ Time Frame: 6 years ]|
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Study of Ocular Blood Flow in Patients With Glaucoma and/or Obstructive Sleep Apnea Syndrome (OSAS)|
|Official Title ICMJE||Study of Ocular Blood Flow Using Laser Doppler Flowmetry in Patients With Glaucoma and/or OSAS|
Obstructive sleep apnea syndrome (OSAS) is a common disease, with a prevalence evaluated between 5 - 7% in the general population. OSAS is characterized by recurrent episodes of partial or complete upper airway obstruction during sleep, which are nearly systematically associated with a desaturation-reoxygenation sequence, an admitted detrimental stimulus for the cardiovascular system. It has now been demonstrated that OSAS per se is able to generate hypertension, atherosclerosis and autonomic dysfunction (high sympathic tone and increase in baseline heart rate), all conditions possibly interacting with ocular vascular regulation. OSAS has major consequences on the ocular level since it is associated with a higher frequency of optic neuropathies, such as glaucoma and nonarteritic ischemic optic neuropathy (NAION), both with functional severe prognosis. Most of vascular changes associated with OSAS have been studied at the level of macrovasculature. In terms of physiopathology, the main effects on the vascular system in OSAS are sympathetic hyperactivity, oxidative stress, development of endothelial dysfunction, systemic inflammation and metabolic alterations such as the appearance of insulin resistance. All these mechanisms can affect the microcirculation of the eye, especially the optic nerve and choroid. Our hypothesis is that the eye microvasculature is affected by OSAS, and these lesions may be detected via a reduced autoregulation of blood flow in humans.
This project aims to demonstrate, quantify, and analyze the vascular modifications of the eye associated with OSAS trough a comparative clinical study on glaucoma patients and OSAS patients and matched healthy subjects for the regulation of the eye blood flow using confocal laser Doppler flowmetry (LDF). The regulation of the ocular blood flow will be assessed using several stimuli and measured using a new confocal LDF.
JUSTIFICATION OF THE PROJECT Obstructive sleep apnea syndrome (OSA) is an under diagnosed disease affecting 5% of the general population. This disease is associated with an increase in the risk for cardiovascular disease (high blood pressure, coronary disease, and stroke). Two optic neuropathies are associated with OSA: glaucoma and nonarteritic anterior ischemic optic neuropathy (NAION). Glaucoma is a frequent progressive optical neuropathy in industrialized countries and one of the leading causes of blindness in the world. Normal tension glaucoma, a vascular form of glaucoma, is the form most frequently associated with OSAS. In addition, in nonglaucomatous OSA patients, there is a diffuse reduction in optic nerve layer thickness correlated with OSA severity, strongly suggesting optic nerve involvement in these patients. Moreover, recent studies have shown that 90% of patients presenting NAION have OSA. These clinical and epidemiological data suggest a causal relation between OSA and the onset of optic neuropathy.
OBJECTIVES: This physiopathological study aims to demonstrate, quantify, and analyze the vascular modifications associated with OSA through:
- A comparative study on glaucoma patients and OSAS patients, with or without NAION, and healthy subjects matched for age, sex, and body mass index: the eye vascular modifications will be quantified using confocal laser Doppler flowmetry.
EXPERIMENTAL SCHEDULE The aim of this study is to characterize ocular blood flow (choroid and optic nerve) regulation in patients in 4 populations: (1) glaucoma patients (2) OSA patients without clinical evidence of optic nerve disease, (3) OSA patients with NAION, (4) matched healthy subjects . OSA patients of group 2 and 3 will be studied 3-6 months after nCPAP treatment.
STUDIED POPULATION :
This clinical project will include OSA patients with the following inclusion criteria: OSA defined by a respiratory-disturbance index > 15/hour (number of episode of partial (hypopnea) or complete (apnea) upper airway obstruction), age between 18 and 80 years, affiliation to the health care system. The exclusion criteria are: ocular disease (including cataract or retinal disease, ametropia > 3 diopters, optic neuropathy other than NAION in group 2), uncontrolled high blood pressure, cardiovascular treatment (vasoconstrictors, vasodilatators, beta and alpha agonists or antagonists, nitric derived medication), corticosteroids, theophylline, sildenafil, immunosuppressors, neuroleptics, non steroid anti inflammatory, oestroprogestative treatment, hypnotics (benzodiazepines), local treatment for ocular hypertension or glaucoma.
Glaucoma was defined as:
Patients were eligible if they had glaucomatous optic nerve head appearance indicative of glaucoma in addition to corresponding visual field loss.
Visual field abnormalitie(s) compatible with glaucomatous damages in accordance to the European guidelines :
Unless one of the following criteria, observed on 2 consecutive automated visual fields (one of these will be the baseline automated visual field: Humphrey 30.2 SITA-Standard strategy):
- A Pattern Standard Deviation (PSD) that occurs in less than 5% of normal fields
Control subjects will be matched with OSA patients for body mass index, gender and age, and will undergo complete overnight polysomnography to discard OSA. Other inclusion and exclusion criteria are similar to that of OSA patients.
MAIN CRITERIA OF EVALUATION AND STATISTICAL ANALYSIS Normalized data during the experiment will be calculated according to baseline data. Changes in blood flow parameters (reflected the vascular reactivity) and correlations will be calculated with nonparametric tests (Friedman and Wilcoxon tests for paired comparisons) using the SPSS 12.0 software. Comparison of OSA group and healthy subjects group will be done using non parametric test (Mann Whitney and Chi 2 test). A two-tailed approach test will determine significance, which is set as p<0.05.
The sensitivity (the minimum statistically significant LDF parameters change (S) that can be detected) will be calculated using the formula : S = (t * SD) / ((square root)n * P mean) * 100, where P mean is the mean value of all measurements, SD the SD of the difference between paired measurement for all subjects, and t the two-tailed value of the t distribution at a 0.05 significance level for n-1-1 degree of freedom.
STRATEGY OF ANALYSIS The clinical experiment aims to compare the vascular regulation of the optic nerve in OSA patients with that of a healthy group of human subjects. Subsequently, a group of OSA patients with NAION will be analyzed in order to compare the ocular blood flow ant its regulation in eyes with ischemic neuropathy (NAION) with eyes of OSA patients without optic nerve disease. All these comparisons will allow to characterize the optic nerve blood flow in healthy eyes, in eyes of OSA patients and in eyes of OSA patients at the time of acute ischemic attack (NAION).The glaucoma patients will be compared with healthy subjects.
ETHICAL ASPECTS This study will be conducted in accordance with the Declaration of Helsinki for research involving human subjects and the Good Clinical Practice guidelines. Informed consent will be obtained from the subjects after explanation of the study. The study protocol was approved by the local Institutional Review Board (Comité de Protection des Personnes, Sud-Est V), declared to the French authorities (insurance : N° contract : 124706 Société Hospitalière d'Assurances Mutuelles Lyon, France).
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
|Condition ICMJE||Obstructive Sleep Apnea Syndrome|
|Intervention ICMJE||Device: measurement of ocular blood flow
measurement of ocular blood flow with a laser Doppler flowmeter
|Study Arms||Experimental: Laser Doppler Flowmetry
Intervention: Device: measurement of ocular blood flow
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Estimated Enrollment ICMJE||90|
|Estimated Completion Date||January 2014|
|Estimated Primary Completion Date||January 2014 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 80 Years (Adult, Senior)|
|Accepts Healthy Volunteers||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||France|
|Removed Location Countries|
|NCT Number ICMJE||NCT00874913|
|Other Study ID Numbers ICMJE||DGS 2006/0052|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||University Hospital, Grenoble|
|Study Sponsor ICMJE||University Hospital, Grenoble|
|Collaborators ICMJE||Not Provided|
|PRS Account||University Hospital, Grenoble|
|Verification Date||October 2012|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP