New MRT Imaging Biomarkers and Treatment With Kinetic Oscillatory Stimulation (KOS) in Nasal Cavity for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Sponsor

Karolinska University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT03502044

Collaborator

(none)

200

Enrollment

Location

Arms

Anticipated Duration (Months)

7.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Placebo controlled trial study of efficacy of Kinetic Oscillation Stimulation (KOS) in nasal cavity will be conducted in patients with myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The outcome of the treatment will be assessed with clinical evaluation of patients, cognitive tests, structural and functional MRI of the brain.

Condition or Disease	Intervention/Treatment	Phase
Myalgic Encephalomyelitis Chronic Fatigue Syndrome	Device: Inactive Kinetic Oscillation Stimulation (KOS) Device: Active Kinetic Oscillation Stimulation (KOS)	N/A

Detailed Description

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a neurologic disease that is characterized by extreme physical and mental fatigue. Although some signs of inflammation have been reported previously in ME/CFS patients, the data have been quite limited and controversial. A recent study based on multiplex array of a Luminex system has demonstrated an immune signature of serum cytokines that is correlated with the disease severity and fatigue duration. Results from resting-state functional MRI (fMRI) studies have also demonstrated that there is a significant correlation between the degree of chronic fatigue and reduction of functional network connectivity in the brain.

The autonomic nervous system (ANS) plays an important role in the regulation of systemic inflammation. The nasal cavity has a rich innervation of cranial nerves. We have recently developed a non-invasive ANS stimulation technique, called Kinetic Oscillation Stimulation (KOS) in the nasal cavity. KOS treatment is expected to have a positive impact on systemic inflammation via the restoration of ANS homeostasis.

With this double blinded, placebo controlled, clinical trial, the efficacy of KOS treatment on ME/CFS will be assessed by clinical evaluation, multiplex immunoassay of peripheral blood samples, performance of psychomotor vigilance task, structural and functional MRI of the brains at the baseline point before KOS treatment and after the completion of KOS treatment period.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double blinded placebo controlled trial design during the first 8 treatments. Single blinded (patient is blinded) controlled trial design during the last 8 treatments.Double blinded placebo controlled trial design during the first 8 treatments. Single blinded (patient is blinded) controlled trial design during the last 8 treatments.

Masking:

Double (Participant, Investigator)

Masking Description:

Both the participants and investigator are blinded with regarding the administration of KOS or placebo treatments during the first 8 treatments. During the following 8 treatments only the patients, not the investigator, are blinded.

Primary Purpose:

Treatment

Official Title:

New MRT Imaging Biomarkers and Treatment With Kinetic Oscillatory Stimulation (KOS) in Nasal Cavity for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Actual Study Start Date :

Apr 17, 2018

Anticipated Primary Completion Date :

Dec 31, 2019

Anticipated Study Completion Date :

Jun 15, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1, active KOS treatment Patients in arm 1 receive active KOS treatment throughout study, which means 16 active KOS treatments. Patients receive KOS treatments twice a week during 8 consecutive weeks.	Device: Active Kinetic Oscillation Stimulation (KOS) 10 minutes active KOS treatment in each nasal cavity.
Placebo Comparator: Arm 2, 8 inactive KOS treatments then 8 active KOS treatments Patients in arm 2 receive inactive KOS treatment during the first 8 KOS treatments of the study. Thereafter patients in arm 2 receive 8 active KOS treatments. Patients receive KOS treatments twice a week during 8 consecutive weeks.	Device: Inactive Kinetic Oscillation Stimulation (KOS) 10 minutes inactive KOS treatment in each nasal cavity. Device: Active Kinetic Oscillation Stimulation (KOS) 10 minutes active KOS treatment in each nasal cavity.

Arm

Intervention/Treatment

Active Comparator: Arm 1, active KOS treatment

Patients in arm 1 receive active KOS treatment throughout study, which means 16 active KOS treatments. Patients receive KOS treatments twice a week during 8 consecutive weeks.

Device: Active Kinetic Oscillation Stimulation (KOS)

10 minutes active KOS treatment in each nasal cavity.

Placebo Comparator: Arm 2, 8 inactive KOS treatments then 8 active KOS treatments

Patients in arm 2 receive inactive KOS treatment during the first 8 KOS treatments of the study. Thereafter patients in arm 2 receive 8 active KOS treatments. Patients receive KOS treatments twice a week during 8 consecutive weeks.

Device: Inactive Kinetic Oscillation Stimulation (KOS)

10 minutes inactive KOS treatment in each nasal cavity.

Device: Active Kinetic Oscillation Stimulation (KOS)

10 minutes active KOS treatment in each nasal cavity.

Outcome Measures

Primary Outcome Measures

Change in Fatigue severity scale [Baseline before KOS intervention, immediately after every second KOS treatment, 3 months after last KOS treatment.]
A 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity according to a self-report scale. The items are scored on a 7 point scale with 1 = strongly disagree and 7= strongly agree. Maximum score possible is 63.

Secondary Outcome Measures

Diagnostic MRI of the brain [At baseline before KOS intervention and within 4 weeks after the last KOS intervention (16 KOS interventions are given during 8 consecutive weeks)]
Functional MRI of the brain at 3T
Signature of systemic inflammation and severity [At baseline before KOS intervention and within 4 weeks after the last KOS intervention (16 KOS interventions are given during 8 consecutive weeks)]
Analysis of high dimensional immune signature from peripheral venous blood samples using mass cytometry.
SF-36 PHYSICAL FUNCTIONING SUBSCALE (PF-10) SF-36 Physical Functioning Subscale (PF-10) [At baseline before KOS intervention, immediately after 8 treatments, immediately after 16 treatments, 3 months after the last treatment.]
The PF-10 is a generic outcome measure designed to examine a person's perceived limitation with physical functioning and is a subscale within the Medical Outcomes Study 36-item Short Form Health Survey (SF-36). There are 10 items, each item is rated on a 3-point scale.
ME/CFS symptom rating scale [At baseline before KOS intervention, immediately after every second KOS treatment, 3 months after last KOS treatment.]
Series of questions regarding ME/CFS symptoms graded 0-5 to evaluate degree of disease burden, according to the diagnostic Canadian Criteria.
Hospital anxiety depression scale (HADS) [At baseline before KOS intervention, immediately after 8 treatments, immediately after 16 treatments, 3 months after the last treatment.]
The questionnaire comprises 7 questions for anxiety and 7 questions for depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression.