Cognitive Behavioral Therapy, Modafinil, or Both for Multiple Sclerosis Fatigue

NCT ID: NCT03621761

Last Updated: 2022-12-27

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

343 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-15

Study Completion Date

2021-11-30

Brief Summary

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This clinical trial will compare the effectiveness of 3 treatments for fatigue in Multiple Sclerosis: 1) a commonly used behavioral treatment strategy (telephone-based cognitive behavioral therapy), 2) a commonly used medication (modafinil), and 3) a combination of both therapies. Each participant will receive one of these 3 treatments for a total of 12 weeks. Hypotheses are that, at 12 weeks, treatment with combination therapy will overall lead to greater reductions in fatigue impact, fatigue severity, and fatigability compared to monotherapy, and that comorbid depression, sleep disturbances, and baseline disability level will be important effect modifiers that influence treatment effect and adherence.

Detailed Description

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Conditions

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Multiple Sclerosis

Keywords

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cognitive behavioral therapy modafinil Provigil fatigue MS

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Rater blinded

Study Groups

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Cognitive Behavioral Therapy

8 weekly telephone-based sessions and 2 booster sessions

Group Type ACTIVE_COMPARATOR

Telephone-based Cognitive Behavioral Therapy

Intervention Type BEHAVIORAL

Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.

Modafinil

50-400 mg per day (oral)

Group Type ACTIVE_COMPARATOR

Modafinil

Intervention Type DRUG

Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).

Cognitive Behavioral Therapy + Modafinil

Telephone-based cognitive behavioral therapy (8 weekly therapy sessions and 2 booster sessions) + Modafinil 50-400 mg per day (oral)

Group Type ACTIVE_COMPARATOR

Telephone-based Cognitive Behavioral Therapy

Intervention Type BEHAVIORAL

Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.

Modafinil

Intervention Type DRUG

Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).

Interventions

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Telephone-based Cognitive Behavioral Therapy

Cognitive behavioral therapy (CBT) is a behavioral-based treatment that promotes effective self-management skills, including adaptive thought processes and behaviors (i.e. "coping skills"). CBT also commonly teaches goal-setting and behavioral activation strategies for engaging in physical, social, and other valued activities in the context of fatigue.

Intervention Type BEHAVIORAL

Modafinil

Modafinil is a safe, well-tolerated and effective wake-promoting agent (oral medication) that is FDA-approved for the treatment of fatigue related to sleep disorders. Modafinil is also one of the most commonly used medications for multiple sclerosis related fatigue in clinical practice, with doses ranging from 50 - 400 mg per day, in divided doses (once to twice daily).

Intervention Type DRUG

Other Intervention Names

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Provigil

Eligibility Criteria

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Inclusion Criteria

1. Patients with clinically definite Multiple Sclerosis (MS, all MS subtypes);
2. Age 18 years or older;
3. Presence of chronic, problematic fatigue that, in the opinion of the patient, has interfered with their daily activities for ≥ 3 months;
4. Average Fatigue Severity Scale (FSS) score greater or equal to 4 at screening.

Exclusion Criteria

1. Current shift work sleep disorder, or narcolepsy diagnosed with polysomnography and multiple sleep latency test
2. History of MS relapse within the last 30 days prior to screening (participants will be considered eligible after the 30-day window);
3. Current stimulant or wake-promoting agent use (such as amantadine, modafinil, methylphenidate, or amphetamine) within 30 days of screening;
4. Pregnancy or breastfeeding;
5. Reliance on hormonal contraception AND concomitant unwillingness to use alternative non-hormonal means of birth control (spermicide or condoms) during the course of the study;
6. Current suicidal ideation (SI) with intent or plan;
7. Known hypersensitivity to modafinil or armodafinil or its inactive ingredients;
8. History of the following cardiovascular conditions: recent myocardial infarction (last 6 months prior to screening), unstable angina, left ventricular hypertrophy, mitral valve prolapse, NYHA class III or IV congestive heart failure;
9. History of prescription or illicit stimulant abuse (such as cocaine, amphetamine, methamphetamine);
10. Any other medical, neurological, or psychiatric condition that, in the opinion of the investigators, could affect participant safety or eligibility.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Washington

OTHER

Sponsor Role collaborator

Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role collaborator

National Multiple Sclerosis Society

OTHER

Sponsor Role collaborator

University of Michigan

OTHER

Sponsor Role lead

Responsible Party

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Tiffany J. Braley, MD, MS

Assistant Professor of Neurology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Tiffany J Braley, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

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The University of Michigan

Ann Arbor, Michigan, United States

Site Status

The University of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Krupp L. Fatigue is intrinsic to multiple sclerosis (MS) and is the most commonly reported symptom of the disease. Mult Scler. 2006 Aug;12(4):367-8. doi: 10.1191/135248506ms1373ed. No abstract available.

Reference Type BACKGROUND
PMID: 16900749 (View on PubMed)

Lerdal A, Celius EG, Krupp L, Dahl AA. A prospective study of patterns of fatigue in multiple sclerosis. Eur J Neurol. 2007 Dec;14(12):1338-43. doi: 10.1111/j.1468-1331.2007.01974.x. Epub 2007 Sep 26.

Reference Type BACKGROUND
PMID: 17903208 (View on PubMed)

Janardhan V, Bakshi R. Quality of life in patients with multiple sclerosis: the impact of fatigue and depression. J Neurol Sci. 2002 Dec 15;205(1):51-8. doi: 10.1016/s0022-510x(02)00312-x.

Reference Type BACKGROUND
PMID: 12409184 (View on PubMed)

Krupp LB, Alvarez LA, LaRocca NG, Scheinberg LC. Fatigue in multiple sclerosis. Arch Neurol. 1988 Apr;45(4):435-7. doi: 10.1001/archneur.1988.00520280085020.

Reference Type BACKGROUND
PMID: 3355400 (View on PubMed)

Smith MM, Arnett PA. Factors related to employment status changes in individuals with multiple sclerosis. Mult Scler. 2005 Oct;11(5):602-9. doi: 10.1191/1352458505ms1204oa.

Reference Type BACKGROUND
PMID: 16193900 (View on PubMed)

Fisk JD, Pontefract A, Ritvo PG, Archibald CJ, Murray TJ. The impact of fatigue on patients with multiple sclerosis. Can J Neurol Sci. 1994 Feb;21(1):9-14.

Reference Type BACKGROUND
PMID: 8180914 (View on PubMed)

Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF. Measuring the functional impact of fatigue: initial validation of the fatigue impact scale. Clin Infect Dis. 1994 Jan;18 Suppl 1:S79-83. doi: 10.1093/clinids/18.supplement_1.s79.

Reference Type BACKGROUND
PMID: 8148458 (View on PubMed)

Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989 Oct;46(10):1121-3. doi: 10.1001/archneur.1989.00520460115022.

Reference Type BACKGROUND
PMID: 2803071 (View on PubMed)

Kroenke K, Spitzer RL, Williams JB. The Patient Health Questionnaire-2: validity of a two-item depression screener. Med Care. 2003 Nov;41(11):1284-92. doi: 10.1097/01.MLR.0000093487.78664.3C.

Reference Type BACKGROUND
PMID: 14583691 (View on PubMed)

Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.

Reference Type BACKGROUND
PMID: 11556941 (View on PubMed)

Braley TJ, Ehde DM, Alschuler KN, Little R, Ng YT, Zhai Y, von Geldern G, Chervin RD, Conroy D, Valentine TR, Romeo AR, LaRocca N, Hamade M, Jordan A, Singh M, Segal BM, Kratz AL. Comparative effectiveness of cognitive behavioural therapy, modafinil, and their combination for treating fatigue in multiple sclerosis (COMBO-MS): a randomised, statistician-blinded, parallel-arm trial. Lancet Neurol. 2024 Nov;23(11):1108-1118. doi: 10.1016/S1474-4422(24)00354-5.

Reference Type DERIVED
PMID: 39424559 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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HUM00143319

Identifier Type: -

Identifier Source: org_study_id