Prevalence and Impact of Obstructive Sleep Apnea in Multiple Sclerosis

Summary

Participation Requirements

Description

BACKGROUND Multiple sclerosis (MS) is an inflammatory demyelinating neurologic disease associated with significant disability. Many pathological mechanisms are believed to drive MS, including inflammation. However, the mechanism behind progression, the major driver of disability in MS, is thought to...

BACKGROUND Multiple sclerosis (MS) is an inflammatory demyelinating neurologic disease associated with significant disability. Many pathological mechanisms are believed to drive MS, including inflammation. However, the mechanism behind progression, the major driver of disability in MS, is thought to be distinctly different. With progression, neurodegeneration and loss of neurons/axons appears to be primarily responsible. A theory of "virtual hypoxia" has been theorized, in that inflammation and demyelination cause neurons and axons to work harder, utilizing more energy. The overuse of neuron/axon energy makes it more likely that there are periods of low/absent energy availability, which drives neuron/axon degeneration and progression in MS. It is well known that MS is associated with sleep apnea. Obstructive sleep apnea (OSA) prevalence in MS patients is approximately 58%. Sleep apnea is a disorder where lower blood oxygenation occurs during sleep. Since it is probable that low blood oxygenation would contribute to neuron/axon injury, we think it is possible MS patients with sleep apnea have worse neurological outcomes (clinically and radiographically). We also anticipate that testing can show an effect on neuron/axon injury as well as inflammation. In addition to MRI changes that correlate with these changes, there are blood markers of neurodegeneration and inflammation including neurofilament-light (NFL) and glial fibrillary acidic protein (GFAP), now available for blood testing commercially. We hypothesize that elevations in such markers may be associated with sleep apnea. We propose to study MS patients with and without sleep apnea by reviewing clinical records of MS clinic patients. This study will enable a first approximation of the prevalence of sleep apnea in MS as well as associated features of the comorbidity. Please note any assessment of prevalence from medical record review is only an approximation. We would also like to conduct a Home Sleep Test sub-study using an at home polysomnagraphy device to help determine an accurate prevalence rate of sleep apnea in the MS population, We will also collect patient questionnaires to gain qualitative data on fatigue, sleepiness, sleep quality, restless leg syndrome risk, pain, sleep apnea risk, depression, and anxiety. Lastly, we would also like to collect blood samples to study markers of neurodegeneration and inflammation. B3. DESCRIPTION OF RESEARCH PROTOCOL A. Study Design - Overview, Methods, Procedures Study Participants Subjects with a confirmed diagnosis of multiple sclerosis will be the inclusion criteria for this study. As patients come to clinic for their routine clinical care visits, we will identify presence of MS. During these visits we will also identify through their medical records those who are pre- treatment for OSA with CPAP (Continuous Positive Airway Pressure) machine and those who are currently on this therapy. We will identify approximately 400 people will take part in this study at Beth Israel Deaconess Medical Center. Approximately 200 people each will take part in this study at UMass Medical Center MS Center and at Lahey MS Center. A total of 800 people will take part in this study at all study sites. Study Procedures Medical Record Review We will collect retrospective data from the patient's medical record including date of birth and demographic data. We will also collect past medical history including medical conditions, surgical history, family history, social history, medications, allergies, as well as the results from prior neurological exams, diagnostic tests, MRIs, previous lab work, and genetic testing. Clinical Information Collection Clinical information from routine clinical care visits will be collected including medical history, surgical history, family history, social history, medications, and allergies. We will also collect other information including vital signs, results from diagnostic tests including lab work and MRIs, neurological exams, neurological and physical functioning assessments on their level of disability, cognitive functioning, hand eye coordination, vision, and walking ability, Questionnaires Questionnaires will be used to assess sleep quality and habits, urinary habits, risk of sleep apnea, fatigue levels, insomnia levels, risk of restless leg syndrome, depression, anxiety, and pain levels. They will take approximately 60 minutes to complete. Body Measurements. We will measure neck size since this is a risk factor for sleep apnea. We will measure height and weight to calculate BMI since obesity is a risk factor for sleep apnea. Blood Sample Collection Blood will be taken at their screening clinical care visit, at month 6, and month 12. The number of samples and the amount of blood collected will vary at each visit but will not exceed 5ml per visit. These samples will be taken for measuring markers of neurodegeneration and inflammation including neurofilament-light (NFL) and glial fibrillary acidic protein (GFAP). Note that at any time during the study, additional blood samples may have to be taken to assess safety or repeat a test. De-identified blood samples will be sent to Quanterix at 113 Hartwell Ave Lexington, Ma 02421 for detection of biomarkers of neurodegeneration and inflammation. Samples will be labeled with subject ID number only. Home Sleep Test We will then have subjects undergo a home sleep test using The Home Sleep Test. The Home Sleep Test (HST) is a device that has an oximeter, a string that goes around the chest to record breaths. A wrist oximeter is a lightweight device that has a wrist band that has sensor to measure oxygen levels in the blood. The HST device also has a lightweight tube which on one end splits into two prongs which are placed in the nostrils for measuring air movement. Within one month of their screening visit, subjects will wear the wrist oximeter and the HST device overnight while subjects sleep and remove them upon waking in the morning. Subjects will only do this once. Subjects then either return the device to the clinic in person or mail the device back using pre-addressed and pre-paid packaging within one week of completing the test. Schedule of Activities Schedule of Study Activities Screening: Informed consent Confirming MS diagnosis Height, weight, neck size measurement Questionnaires: Sleep History (NDSQ), STOP-BANG, Berlin, Modified Fatigue Impact Scale (MFIS), Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Restless Legs Syndrome-Diagnostic Index (RLS-DI), Pain Scale (NRS), and Hospital Anxiety and Depression Scale (HADS) Blood draw Within 1 month of screening • Home Sleep Study Month 6: Questionnaires: STOP-BANG, Berlin, MFIS, FSS, ESS, ISI, PSQI, RLS-DI, and HADS Blood draw Month 12 Questionnaires: STOP-BANG, Berlin, MFIS, FSS, ESS, ISI, PSQI, RLS-DI, and HADS Blood draw Data Analysis • Data will be analyzed continually over the course of this study. Once HST data is collected we will determine sleep apnea prevalence and severity. We will correlate this with questionnaire findings as well as HST metrics, clinical metrics of MS disease activity/disability. We will also assess blood and MRI testing on an ongoing basis in a similar manner. Research Activities as Coordinating Site: The coordinating site will train the other involved sites in accordance with the protocol. All sites will have a copy of our IRB approved protocol. We will communicate with the other sites on an as needed basis regarding updates to the protocol or any other changes to the study. Any retraining will be performed if requested. The coordinating site will provide questionnaires, checklists, and materials related to completion of the proposed work. The coordinating site will disseminate funds as required from any grant associated with this work. The coordinating site will be in charge of collecting and storing all data for the proposed study. This data includes clinical and demographic data as well as laboratory and radiological data. The coordinating site will record any deviations and adverse events related to the protocol. The principle investigator will oversee all unanticipated problems, adverse events, noncompliance, and new information about the study will be report them to the other sites immediately. B. Statistical Considerations Sample Size Justification: All of Dr. Sloane's current MS patients are eligible to be screened for this study. The sample size will be 400 patients from Beth Israel Deaconness Medical center, 200 from Lahey Clinic, and 200 from UMASS for 800 patients total. Data Analysis: All data will be collected and stored using Microsoft Excel on a secure computer. Data analysis will be conducted by utilizing Harvard Catalyst biostatistician services. Statistical analyses used will be up to the discretion of the biostatistician and team. C. Subject Selection We will use electronic medical records from Dr. Sloane's patients to identify patients with MS and distinguish those who are either on CPAP therapy or not. Since patients with or without obstructive sleep apnea will be considered for the study, all of Dr. Sloane's patients are eligible. B4. POSSIBLE BENEFITS There is no direct benefit to the patient from being in this study. However, patients' participation may help others in the future as a result of knowledge gained from this database. B5. POSSIBLE RISKS AND ANALYSIS OF RISK/BENEFIT RATIO There are minimal risks associated with this medical record review, which include a breach of confidentiality. The risk that someone other than the patient's physician and the MS treatment team will be able to link the patient's information to the study with the patient's name is minimal. The information that we receive will be kept in a secure, password-protected computer within the MS team's research drive. Some of the questions asked as part of the study, may make the patient feel uncomfortable. They may refuse to answer any of the questions. Although not ideal for purposes of this study, refusing to answer questions/questionnaires is permissible. HST devices are used as a diagnostic tool routinely in clinical practice for sleep apnea and are FDA approved for this indication. Complications are rare and not high-risk. The most common side effect is skin irritation caused by the adhesive used to attach test sensors to the skin. Risk of blood draw may include discomfort, bruising, and very rarely infection at the site where the needle enters the skin. Patients may also possibly experience dizziness, nausea, or fainting during blood collection RECRUITMENT Subjects will be identified via medical record review. Any subject data included in the study will be a result of the subject matching the inclusion criteria. Consent Written Consent The PI on this study has requested a HIPPA Waiver of Authorization due to the fact that this is a retrospective medical record review. An informed consent will be signed for the HST device substudy. Verbal Consent Prior to any data collection under this protocol for patients restricted to telemedicine visits due to COVID-19, a verbal consent will be obtained using a verbal consent script. An information sheet will be sent to the patient by email or by mail. Written consent can be obtained if/when subjects come to the medical center for in person visits. Subject Protection No subjects in this study will be vulnerable to coercion or undue influence because this is a retrospective medical record review. However, since this study does involve the use of PHI, every effort will be maintained to de-identify PHI to maintain confidentiality. In addition, each subject will be given a unique identifier (i.e. 001) and the codebreaker will be located in a secure, locked office

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