Open-Label Placebos to Treat Fatigue in Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT04002102
• Recruitment Status: Completed
• First Posted: June 28, 2019
• Last Update Posted: February 1, 2022
• Sponsor: University of Alabama at Birmingham
• Information provided by (Responsible Party): Tapan Shirish Mehta, University of Alabama at Birmingham

Study Description

Brief Summary:

Fatigue is one of the most prevalent and disabling symptoms of multiple sclerosis. Current treatments, including pharmacological, physical therapy, sleep regulation and psychological interventions are of marginal benefit. Pharmacological treatments have inconsistent evidence. Recent studies show that non-deceptive open-label placebos (OLP) have moderate-to-large effects on symptoms, including fatigue, in adults with a variety of medical conditions.

Hence, this is a pilot and feasibility study to obtain data on the feasibility and effects of OLP for multiple sclerosis related fatigue and its impact to provide the basis for a competitive NIH application. This pilot study will be the first study to evaluate whether OLP, that garners full consent and engages patients in their wellness, may offer a safe, effective treatment for multiple sclerosis related fatigue.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis; Fatigue	Other: OLP treatment; Other: Usual care; Other: Expectancy Group	Not Applicable

Detailed Description:

The purpose of this pilot study is to evaluate the feasibility of recruiting, enrolling and retaining participants in a study on the acceptability and effects of a non-deceptive (open-label) administration of placebo pills for treating MS related fatigue. Specific Aim 1 will assess the feasibility endpoints including accrual (enroll 44 participants), retention (80% of the sample) and placebo adherence (90%). Specific Aim 2 will evaluate the between-group changes in fatigue, quality of life, cognitive functioning and self-efficacy. Specific Aim 3 will evaluate participant acceptability, satisfaction and experience.

Design:

This pilot study is a randomized control trial consisting of three arms: open label placebo arm, expectancy arm, and usual care arm. The clinical coordinator will review medical records, enroll and consent participants based on the following inclusion criteria: diagnosis of MS, 19 years or older, report of moderate to severe fatigue, PDDS score of < 7, and stable dose of DMTs for 90 days.

Exclusion criteria consists of: major comorbid conditions and use of off label medications or exercise programs in the past 30 days, and if one is confined to a wheelchair.

Baseline and 21 day tele assessments will involve objective measures performed by a physical therapist, Single Digit Modality Test (SDMT) and Five Time Sit to Stand (FTSST) and subjective questionnaires sent to participant's email including Modified Fatigue Impact Scale (MFIS), Functional Systems Score (FSS), Patient Reported Outcomes Measurement Information System (PROMIS), Perceived Deficits Questionnaire, Epworth Sleepiness Scale, and the SF-36 assess of quality of life. Participants will be randomized by the clinical coordinator after baseline testing. The open label placebo and expectancy arm will meet with the care provider who will follow a scripted orientation that mimics a typical patient-provider interaction when prescribing a medication, including the rationale for effectiveness. The provider will emphasize the importance of adherence to the medication for the open label placebo arm and the breathing exercises for the expectancy arm for the next 21 days. A tracking sheet will be provided to both arms to document adherence. The usual care arm will meet with the care provider who will follow a scripted orientation on fatigue and heat management strategies. All participants will receive educational materials on fatigue and heat management. A day 11 check in call will be made to gauge progress and answer questions. After the 21 day tele assessment is performed, the participant will complete subjective questionnaires via email for 28 day and 35 day follow up.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Open-Label Placebos to Treat Fatigue in Multiple Sclerosis
• Actual Study Start Date: February 17, 2020
• Actual Primary Completion Date: January 19, 2022
• Actual Study Completion Date: January 19, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: OLP treatment; Participants randomized to the treatment group will receive: 1) educational materials; 2) positive expectancy; 3) 2 placebo pills twice a day for 21 days.	Other: OLP treatment; Receive two open-label placebo pills twice a day after randomization. Will receive for 21 days and then stop. It will include educational materials and positive expectancy.; Other Names: Open-Label placebo; Glucose Tablet
Usual care; Participants randomized to the no treatment group will remain in standard care alone for 21 days and receive educational materials.	Other: Usual care; Remain in standard care after randomization and educational materials.; Other Name: Standard care
Active Comparator: Expectancy Group; Participants receive educational materials and positive expectancy orientation via Zoom or telephone	Other: Expectancy Group; Educational materials and positive expectancy orientation via Zoom or telephone; Other Name: Education

Outcome Measures

Primary Outcome Measures :

1. Change from baseline fatigue at 21 days using the Fatigue Severity Scale (FSS). [ Time Frame: Participants will complete this scale at baseline and 21 days later, the participant will spend 10 minutes each assessment completing this scale. ]
   This scale is used to measure fatigue and the scale has a range from 9-63 with 9 being the best possible score and 63 being the worst score.
2. Change from baseline impact of fatigue at 21 days using the Modified Fatigue Impact Scale (MFIS). [ Time Frame: Participants will complete this scale at baseline and 21 days later, the participant will spend 15 minutes each assessment completing this scale. ]
   This scale is used to measure fatigue and the scale has a range from 0 to 84 with 0 being the best possible score and 84 being the worst score.
3. Change from baseline quality of life at 21 days using the 36-item Short Form survey (SF-36). [ Time Frame: Participants will complete this scale at baseline and 21 days later, the participant will spend 15 minutes each assessment completing this scale. ]
   The scores for this survey range from 0-100 with 0 being the worst possible score and 100 being the best possible score.

Secondary Outcome Measures :

1. Change from baseline sleepiness at 21 days using the Epworth Sleepiness Scale (ESS). [ Time Frame: Participants will complete this scale at baseline and 21 days later, the participant will spend 15 minutes each assessment completing this scale. ]
   This scale is used to measure sleepiness and the scale has a range from 0-24 with 0 being the best possible score and 24 being the worst.
2. Change from baseline neurological functioning at 21 days using the Perceived Deficit Questionnaire 5-Item Version (PDQ-5). [ Time Frame: Participants will complete this scale at baseline and 21 days later, the participant will spend 15 minutes each assessment completing this scale. ]
   The scores for this questionnaire range from 5-25 with 5 being the best possible score and 25 being the worst possible score.
3. Godin Leisure-Time Exercise Questionnaire [ Time Frame: Participants will complete this scale at baseline and 21 days later ]
   A self-explanatory, brief four-item query of usual leisure-time exercise habits

Other Outcome Measures:

1. Change from baseline general self efficacy for managing chronic conditions at 21 days using the PROMIS instrument [ Time Frame: Participants will complete this scale at baseline and 21 days later, the participant will spend 15 minutes each assessment completing this scale. ]
   The scores for this tool are coded separately for each of the 10 questions and range from 1-5 for questions Global01-06, 08r, 09r, and 10r with 1 being the worst possible score and 5 being the best possible score and a range from 0-10 for question Global07r with 0 being the worst possible score and 10 being the best possible score.

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• A diagnosis of MS
• Aged 19 years or older
• report moderate-to-severe fatigue (i.e., ≥4 on the FSS)
• Patient Determined Disease Steps score of ≥7.

Exclusion Criteria:

• Major comorbid conditions that might influence fatigue (e.g. lupus, chronic fatigue syndrome)
• Patients treated with off label medications or exercise program in the past 30 days.

Contacts and Locations

Locations

United States, Alabama

Tanner Foundation

Birmingham, Alabama, United States, 35209

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

Sponsors and Collaborators

University of Alabama at Birmingham

Investigators

• Principal Investigator: Tapan S Mehta, PhD; University of Alabama at Birmingham

More Information

• Responsible Party: Tapan Shirish Mehta, Principal Investigator, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT04002102
• Other Study ID Numbers: IRB-300003575
• First Posted: June 28, 2019
• Last Update Posted: February 1, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: To be determined. Sharing study protocol, statistical analysis plan, and informed consent.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: Will be posted on CT.gov
• Access Criteria: To be determined

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tapan Shirish Mehta, University of Alabama at Birmingham:

Placebo; Open-Label

Additional relevant MeSH terms:

Multiple Sclerosis; Sclerosis; Fatigue; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases