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

NCT03621761 | Completed Phase 4 Results FDA Drug

• 1 other identifier: HUM00143319
• Study Type: interventional
• Target: 343
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Multiple Sclerosis

Keywords

cognitive behavioral therapy; modafinil; Provigil; fatigue; MS

Outcome Measures

Primary Outcomes (1)

• Change in the Modified Fatigue Impact Scale (MFIS) Score

  The Modified Fatigue Impact Scale is a 21-item self-report survey. Each item is rated 0-4, Total scores range from 0-84. . Higher scores indicate a greater impact of fatigue on a person's activities. The primary outcome measure will be the mean within-subject difference between baseline and 12-week Modified Fatigue Impact Scale values (delta-MFIS), compared between the 3 treatment groups.

  Baseline-12 weeks

Secondary Outcomes (3)

• Change in Fatigue Intensity as Assessed by Self-reported Numerical Rating Scale (NRS) Score.

  Baseline-12 weeks

• Change in Fatigue Interference as Assessed by Self-reported Numerical Rating Scale (NRS) Score

  Baseline-12 weeks

• Change in Fatigability as Assessed by the Self-reported Fatigue Intensity Numerical Rating Scale (NRS) Score and Physical Activity Level

  Baseline-12 weeks

Study Arms (3)

Cognitive Behavioral Therapy

ACTIVE COMPARATOR

8 weekly telephone-based sessions and 2 booster sessions

Behavioral: Telephone-based Cognitive Behavioral Therapy

Modafinil

ACTIVE COMPARATOR

50-400 mg per day (oral)

Drug: Modafinil

Cognitive Behavioral Therapy + Modafinil

ACTIVE COMPARATOR

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

Behavioral: Telephone-based Cognitive Behavioral Therapy; Drug: Modafinil

Interventions

Telephone-based Cognitive Behavioral Therapy 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.

Cognitive Behavioral Therapy; Cognitive Behavioral Therapy + Modafinil

Modafinil 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).

Also known as: Provigil

Cognitive Behavioral Therapy + Modafinil; Modafinil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Current shift work sleep disorder, or narcolepsy diagnosed with polysomnography and multiple sleep latency test
• History of MS relapse within the last 30 days prior to screening (participants will be considered eligible after the 30-day window);
• Current stimulant or wake-promoting agent use (such as amantadine, modafinil, methylphenidate, or amphetamine) within 30 days of screening;
• Pregnancy or breastfeeding;
• 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;
• Current suicidal ideation (SI) with intent or plan;
• Known hypersensitivity to modafinil or armodafinil or its inactive ingredients;
• 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;
• History of prescription or illicit stimulant abuse (such as cocaine, amphetamine, methamphetamine);
• Any other medical, neurological, or psychiatric condition that, in the opinion of the investigators, could affect participant safety or eligibility.

Sponsors & Collaborators

• University of Michigan: lead
• University of Washington: collaborator
• Patient-Centered Outcomes Research Institute: collaborator
• National Multiple Sclerosis Society: collaborator

Study Sites (2)

The University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

The University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (11)

• 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.

  PMID: 16900749 BACKGROUND

• 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.

  PMID: 17903208 BACKGROUND

• 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.

  PMID: 12409184 BACKGROUND

• 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.

  PMID: 3355400 BACKGROUND

• 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.

  PMID: 16193900 BACKGROUND

• 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.

  PMID: 8180914 BACKGROUND

• 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.

  PMID: 8148458 BACKGROUND

• 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.

  PMID: 2803071 BACKGROUND

• 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.

  PMID: 14583691 BACKGROUND

• 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.

  PMID: 11556941 BACKGROUND

• 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.

  PMID: 39424559 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Fatigue

Interventions

Modafinil

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Tiffany Braley
• Organization: University of Michigan

tbraley@med.umich.edu

734-232-1147

Study Officials

• Tiffany J Braley, MD, MS

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Rater blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Study Record Dates

• First Submitted: August 3, 2018
• First Posted: August 8, 2018
• Study Start: November 15, 2018
• Primary Completion: August 24, 2021
• Study Completion: November 30, 2021
• Last Updated: December 27, 2022
• Results First Posted: December 27, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)