Continuous Positive Airway Pressure (CPAP) for Fatigue in Patients With Multiple Sclerosis (MS) and Obstructive Sleep Apnea (OSA)

NCT ID: NCT01563900

Last Updated: 2013-04-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-29

Study Completion Date

2016-02-29

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Fatigue is a symptom present in 76 to 92% of people with multiple sclerosis (MS). Fatigue is usually described as an overwhelming sense of tiredness, lack of energy, and feeling of exhaustion which is different from sleepiness. Fatigue is also a symptom commonly seen in people with obstructive sleep apnea (OSA). The overall objective is to develop a non-pharmacological treatment for fatigue in MS. The objective of this study is to evaluate if treatment of OSA with continuous positive airway pressure (CPAP) improves fatigue in MS subjects with OSA and fatigue. This will be a small pilot randomized, double-blind, sham-controlled clinical trial; the control group will be treated with a sham-CPAP machine and intervention group will be treated with an auto-titration CPAP machine. The primary outcome measure will be improvement (decrease) in the Modified Fatigue Impact Scale from baseline. The duration of intervention will be 12 weeks to achieve a clinical response in the treatment group. After this intervention participants in both groups will be offered a referral to the sleep clinic of their preference for formal treatment as per standard of care.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Multiple sclerosis (MS) is a demyelinating inflammatory disease that is one of the most common neurological causes of disability in young adults. Besides physical disability, fatigue is a very common symptom present in 76 to 92% of people with MS. The 1998 Multiple Sclerosis Council for clinical practice guidelines published a consensus definition: subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with the usual and desired activity. Although fatigue may be difficult to differentiate from sleepiness, it is a clinically different symptom. Sleepiness is the tendency to fall asleep or doze off. Some reports that the prevalence of moderate to severe sleep problems in MS is significantly higher than in the general population 51.5% vs 33.1%. It has also been reported that poor sleep can correlate with depression in subject with MS. Few studies have examined the effect of stimulants, amantadine or modafinil for treatment of fatigue and have shown contradictory data as effective treatments in MS patients.

Obstructive sleep apnea (OSA) has also been seen described in MS. Few case reports studies have reported that MS patients with OSA treated with continuous positive airway pressure (CPAP) had improvement in fatigue but not quality of life. Although the prevalence of OSA in the MS population is unknown, it may as much as twice as common as in the general population, which is 3 to 7%. Aside from the increased risk of daytime sleepiness, mood disorders, cardiovascular risk factors and accidents, OSA has also been implicated in increasing inflammatory markers like tumor necrosis factor (TNF-α). Elevation in TNF-α has also been seen in MS patients complaining of fatigue, which is thought to play a role in pathophysiology of fatigue in MS. The rational of this study is to determine if treatment of OSA with CPAP in MS patients improves fatigue. If effective, CPAP may not only decrease the risk of long term complications but may also improve the quality of life and daily living of these patients.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Fatigue Multiple Sclerosis Sleep Apnea

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

sham-CPAP group

The sham-CPAP device will be set at 4 centimeters of water pressure (cwp).

Group Type SHAM_COMPARATOR

Sham-CPAP

Intervention Type DEVICE

The sham-CPAP device will be set at 4 centimeters of water pressure (cwp). An exhalation connector will be place between the mask interface and the tubing without the enlarged port to maintain blinding; the final pressure delivered to the participant will be 2 cwp.

Auto-titration CPAP

This group will received an auto-titration CPAP, which will have a pressure range of 5 to 15 cwp. This device delivers pressure as needed by the patient at any given time while using the device.

Group Type ACTIVE_COMPARATOR

Auto-titration CPAP

Intervention Type DEVICE

An auto-titration CPAP will be set at a pressure between 5 to 15 cwp. This device delivers pressure as needed by the patient at any given time while using the device.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Auto-titration CPAP

An auto-titration CPAP will be set at a pressure between 5 to 15 cwp. This device delivers pressure as needed by the patient at any given time while using the device.

Intervention Type DEVICE

Sham-CPAP

The sham-CPAP device will be set at 4 centimeters of water pressure (cwp). An exhalation connector will be place between the mask interface and the tubing without the enlarged port to maintain blinding; the final pressure delivered to the participant will be 2 cwp.

Intervention Type DEVICE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Respironics CPAP device will be used. Respironics CPAP device

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 18-65 years old
* Diagnosis of clinical MS as defined by the 2010 McDonald criteria
* Have either relapsing remitting, primary progressive or secondary progressive forms of MS
* expanded disability status scale ≤5
* Complaint of fatigue defined subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with the usual and desired activity.
* Berlin questionnaire score of ≥2 35
* Mild to moderate OSA defined as Apnea hypopnea index (AHI) of ≥ 5 and \< 30 events/hour on baseline ambulatory PSG

Exclusion Criteria

* Prior diagnosis, past or current treatment for sleep related breathing disorder
* Severe sleep apnea defined as AHI ≥ 30 events/hour on baseline ambulatory PSG,
* Prior diagnosis of restless leg syndrome, parasomnias, insomnia, and narcolepsy
* Prior diagnosis of pulmonary disease: asthma, chronic obstructive pulmonary disease and bronchiectasis
* Diagnosis of clinical depression or Center for epidemiologic studies-depression scale(CES-D)score of ≥ 16 36,37
* An acute MS exacerbation in the last 3 months. If patient has an acute exacerbation during the study, the patient will be excluded from the study as this can be a cause fatigue
* Started on any disease modifying treatment (either primary or second line agents) or have switched to a second therapy in the last 6 month poor sleep and fatigue can be side effects.
* Current use of sedative-hypnotics medications, tricyclic, antidepressants, or trazodone.
* Started or change in dose within the last 3 months of amantadine, modafinil, armodafinil, or other stimulating agent for MS related fatigue
* Pregnancy
* Unstable medical or psychiatric condition
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Northwestern University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Dr. Hryar Attarian

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Hrayr Attarian, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Northwestern UNiversity, Department of Neurology

Chicago, Illinois, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Krupp LB, Coyle PK, Doscher C, Miller A, Cross AH, Jandorf L, Halper J, Johnson B, Morgante L, Grimson R. Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo. Neurology. 1995 Nov;45(11):1956-61. doi: 10.1212/wnl.45.11.1956.

Reference Type BACKGROUND
PMID: 7501140 (View on PubMed)

Reder AT, Antel JP. Clinical spectrum of multiple sclerosis. Neurol Clin. 1983 Aug;1(3):573-99.

Reference Type BACKGROUND
PMID: 6095009 (View on PubMed)

Krupp LB, Serafin DJ, Christodoulou C. Multiple sclerosis-associated fatigue. Expert Rev Neurother. 2010 Sep;10(9):1437-47. doi: 10.1586/ern.10.99.

Reference Type BACKGROUND
PMID: 20819014 (View on PubMed)

Shahid A, Shen J, Shapiro CM. Measurements of sleepiness and fatigue. J Psychosom Res. 2010 Jul;69(1):81-9. doi: 10.1016/j.jpsychores.2010.04.001.

Reference Type BACKGROUND
PMID: 20630266 (View on PubMed)

Attarian HP, Brown KM, Duntley SP, Carter JD, Cross AH. The relationship of sleep disturbances and fatigue in multiple sclerosis. Arch Neurol. 2004 Apr;61(4):525-8. doi: 10.1001/archneur.61.4.525.

Reference Type BACKGROUND
PMID: 15096400 (View on PubMed)

Bamer AM, Johnson KL, Amtmann DA, Kraft GH. Beyond fatigue: Assessing variables associated with sleep problems and use of sleep medications in multiple sclerosis. Clin Epidemiol. 2010 May 1;2010(2):99-106. doi: 10.2147/CLEP.S10425.

Reference Type BACKGROUND
PMID: 20838467 (View on PubMed)

Merlino G, Fratticci L, Lenchig C, Valente M, Cargnelutti D, Picello M, Serafini A, Dolso P, Gigli GL. Prevalence of 'poor sleep' among patients with multiple sclerosis: an independent predictor of mental and physical status. Sleep Med. 2009 Jan;10(1):26-34. doi: 10.1016/j.sleep.2007.11.004. Epub 2008 Jan 22.

Reference Type BACKGROUND
PMID: 18207453 (View on PubMed)

Rammohan KW, Rosenberg JH, Lynn DJ, Blumenfeld AM, Pollak CP, Nagaraja HN. Efficacy and safety of modafinil (Provigil) for the treatment of fatigue in multiple sclerosis: a two centre phase 2 study. J Neurol Neurosurg Psychiatry. 2002 Feb;72(2):179-83. doi: 10.1136/jnnp.72.2.179.

Reference Type BACKGROUND
PMID: 11796766 (View on PubMed)

Jackson ML, Stough C, Howard ME, Spong J, Downey LA, Thompson B. The contribution of fatigue and sleepiness to depression in patients attending the sleep laboratory for evaluation of obstructive sleep apnea. Sleep Breath. 2011 Sep;15(3):439-45. doi: 10.1007/s11325-010-0355-2. Epub 2010 May 6.

Reference Type BACKGROUND
PMID: 20446116 (View on PubMed)

Kohli P, Balachandran JS, Malhotra A. Obstructive sleep apnea and the risk for cardiovascular disease. Curr Atheroscler Rep. 2011 Apr;13(2):138-46. doi: 10.1007/s11883-011-0161-8.

Reference Type BACKGROUND
PMID: 21253882 (View on PubMed)

Tamaki S, Yamauchi M, Fukuoka A, Makinodan K, Koyama N, Tomoda K, Yoshikawa M, Kimura H. Production of inflammatory mediators by monocytes in patients with obstructive sleep apnea syndrome. Intern Med. 2009;48(15):1255-62. doi: 10.2169/internalmedicine.48.2366. Epub 2009 Aug 3.

Reference Type BACKGROUND
PMID: 19652426 (View on PubMed)

Heesen C, Nawrath L, Reich C, Bauer N, Schulz KH, Gold SM. Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour? J Neurol Neurosurg Psychiatry. 2006 Jan;77(1):34-9. doi: 10.1136/jnnp.2005.065805.

Reference Type BACKGROUND
PMID: 16361589 (View on PubMed)

Kaminska M, Kimoff RJ, Benedetti A, Robinson A, Bar-Or A, Lapierre Y, Schwartzman K, Trojan DA. Obstructive sleep apnea is associated with fatigue in multiple sclerosis. Mult Scler. 2012 Aug;18(8):1159-69. doi: 10.1177/1352458511432328. Epub 2011 Dec 19.

Reference Type BACKGROUND
PMID: 22183937 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

STU00052358

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Sleep for Stroke Management and Recovery Trial
NCT03812653 ACTIVE_NOT_RECRUITING NA
Sleep Apnea Treatment After Stroke (SATS)
NCT00282815 TERMINATED PHASE2