Treatment of Fatigue With Methylphenidate, Modafinil and Amantadine in Multiple Sclerosis (TRIUMPHANT-MS)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03185065 |
|
Recruitment Status :
Completed
First Posted : June 14, 2017
Results First Posted : October 19, 2020
Last Update Posted : October 20, 2020
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Fatigue in Multiple Sclerosis | Drug: Amantadine Drug: Modafinil Drug: Methylphenidate Drug: Placebos | Phase 3 |
This is a randomized, placebo-controlled, crossover, 4-sequence, 4-period, double-blind (participants and investigators), multicenter trial of 3 commonly used medications for treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS defined by McDonald Criteria.
Using a balanced Latin-square crossover design, subjects will be allocated, in a double-blind, randomized fashion, to one of the four treatment sequences (Figure 1): 1) amantadine, placebo, modafinil, methylphenidate; 2) placebo, methylphenidate, amantadine, modafinil; 3) modafinil, amantadine, methylphenidate, placebo; and 4) methylphenidate, modafinil, placebo and amantadine. Each medication will be titrated over four weeks to the participants' highest tolerated dose or the pre-defined highest dose. The dosing and titration schedule of the study medications are depicted in Figure 2. Each treatment period will be 6 weeks and there will be a 2-week washout period between each treatment period. At the beginning of the trial, a biostatistician at University of California, San Francisco (UCSF) will prepare a concealed allocation schedule, randomly assigning the four sequences, in blocks of 4, to a consecutive series of numbers and at the time of enrollment, each participant will be assigned the next consecutive number (and hence the sequence of study medications).
The primary endpoint of the study will be fatigue severity as measured by the MFIS score, between 26th and 35th day of each treatment period (while the patient is taking the maximal tolerated or target dose). The MFIS is a validated patient-reported outcome. The questionnaire will be administered remotely (through internet, phone or mailed forms) and the participants can answer the questions in few minutes while at home or at their work place. The questionnaire has been validated in English and Spanish.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 141 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Intervention Model Description: | randomized, placebo-controlled, crossover, 4-sequence, 4-period, double-blind, multicenter trial of 3 commonly used medications for treatment of Multiple Sclerosis related fatigue versus placebo in fatigued subjects with MS. |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | Double-blind |
| Primary Purpose: | Treatment |
| Official Title: | Treatment of Fatigue With Methylphenidate, Modafinil and Amantadine in Multiple Sclerosis |
| Actual Study Start Date : | October 4, 2017 |
| Actual Primary Completion Date : | November 21, 2019 |
| Actual Study Completion Date : | November 21, 2019 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Arm A
amantadine, placebo, modafinil, methylphenidate
|
Drug: Amantadine
100 mg of amantadine increased to 200 mg of amantadine, if tolerated Drug: Modafinil 100 mg of modafinil increased to 200 mg of modafinil, if tolerated Drug: Methylphenidate 5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated Drug: Placebos 1 placebo capsule increased to max of 2 capsules twice daily |
|
Experimental: Arm B
placebo, methylphenidate, amantadine, modafinil
|
Drug: Amantadine
100 mg of amantadine increased to 200 mg of amantadine, if tolerated Drug: Modafinil 100 mg of modafinil increased to 200 mg of modafinil, if tolerated Drug: Methylphenidate 5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated Drug: Placebos 1 placebo capsule increased to max of 2 capsules twice daily |
|
Experimental: Arm C
modafinil, amantadine, methylphenidate, placebo
|
Drug: Amantadine
100 mg of amantadine increased to 200 mg of amantadine, if tolerated Drug: Modafinil 100 mg of modafinil increased to 200 mg of modafinil, if tolerated Drug: Methylphenidate 5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated Drug: Placebos 1 placebo capsule increased to max of 2 capsules twice daily |
|
Experimental: Arm D
methylphenidate, modafinil, placebo and amantadine
|
Drug: Amantadine
100 mg of amantadine increased to 200 mg of amantadine, if tolerated Drug: Modafinil 100 mg of modafinil increased to 200 mg of modafinil, if tolerated Drug: Methylphenidate 5 mg of methylphenidate uptitrated to max of 20 mg of methylphenidate, if tolerated Drug: Placebos 1 placebo capsule increased to max of 2 capsules twice daily |
- Modified Fatigue Impact Scale (MFIS) Score [ Time Frame: Week 5 of each treatment period ]MFIS score during the fifth week of treatment period. The total score of the MFIS ranges from 0 to 84. Higher scores denote more severe fatigue.
- Quality of Life in Neurological Disorders (Neuro-QoL) Item Bank - Fatigue Score [ Time Frame: Week 5 of each treatment period ]Neuro-QoL Item Bank - Fatigue T score during the fifth week of treatment period. T-score distributions rescale raw scores into standardized scores with a mean of 50 and a standard deviation (SD) of 10. Higher T-scores denote more severe fatigue.
- Epworth Sleepiness Scale (ESS) Score [ Time Frame: Week 5 of each treatment period ]ESS score during the fifth week of treatment period. The ESS score can range from 0 to 24. The higher the score, the higher that person's average sleep propensity in daily life, or their 'daytime sleepiness'.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion criteria:
- Age 18 years and older.
- Females of childbearing age must have a negative urine pregnancy test at baseline and use an effective method of contraception during the study.
- Diagnosis of MS (according to the 2010 McDonald criteria).
- Expanded Disability Status Scale (EDSS) score at the time of screening 0.0-7.0.
- Fatigue reportedly present and screening Modified Fatigue Impact Scale (MFIS) score more than 33.
- At least a two-week washout for any fatigue-related drug, including study medications.
Exclusion criteria:
- Neurodegenerative disorders other than relapsing or progressive MS.
- Breastfeeding or pregnant.
- History of coronary artery disease or congestive heart failure.
- Uncontrolled hypertension at screening (history of high blood pressure and screening systolic blood pressure >160 or diastolic blood pressure>100).
- Glomerular Filtration Rate (GFR) (glomerular filtration rate) < 50.
- Abnormal liver function at screening (AST or Alanine Aminotransferase (ALT) more than twice the upper limit of normal).
- Terminal medical conditions.
- Currently treated for active malignancy.
- Planned surgery or move within 8 months of screening.
- Alcohol or substance abuse in the past year (except marijuana or other cannabinoids).
- A history of intolerance or allergic or anaphylactic reaction to amantadine, modafinil, methylphenidate or any component of the preparation.
- Clinically unstable medical or psychiatric disorders that require acute treatment as determined by the PI.
- Concurrent use of monoamine oxidase inhibitors-B.
- Hypersensitivity/idiosyncrasy to sympathomimetic amines
- Inability to communicate or answer the questionnaires in English or Spanish.
- Severe untreated anemia (blood hemoglobin <9gr/dl)
- History of untreated hypothyroidism
- History of untreated sleep apnea
- History of long QT syndrome, atrial fibrillation or tachyarrhythmias (other than sinus tachycardia)
- History of ischemic or hemorrhagic stroke
- History of glaucoma
- History of Tourette syndrome
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03185065
| United States, California | |
| University of California San Francisco | |
| San Francisco, California, United States, 94158 | |
| United States, Maryland | |
| Johns Hopkins University | |
| Baltimore, Maryland, United States, 21287 | |
| Principal Investigator: | Bardia Nourbakhsh, MD | Johns Hopkins University |
Documents provided by Johns Hopkins University:
| Responsible Party: | Johns Hopkins University |
| ClinicalTrials.gov Identifier: | NCT03185065 |
| Other Study ID Numbers: |
IRB00119702 |
| First Posted: | June 14, 2017 Key Record Dates |
| Results First Posted: | October 19, 2020 |
| Last Update Posted: | October 20, 2020 |
| Last Verified: | October 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
|
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 Amantadine Methylphenidate Modafinil Central Nervous System Stimulants Physiological Effects of Drugs |
Dopamine Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Dopamine Agents Neurotransmitter Agents Wakefulness-Promoting Agents Cytochrome P-450 CYP3A Inducers Cytochrome P-450 Enzyme Inducers Antiparkinson Agents Anti-Dyskinesia Agents Antiviral Agents Anti-Infective Agents Analgesics, Non-Narcotic Analgesics |