ACTH for Fatigue in Multiple Sclerosis Patients

Phase 3

Completed

Conditions: Multiple Sclerosis, Relapsing-Remitting

Interventions: Drug: ACTH
Drug: Placebo

Registration Number: NCT02315872

Lead Sponsor: Providence Health & Services

Brief Summary: This is a study of Acthar gel (ACTH) in patients with relapsing multiple sclerosis who are experiencing chronic fatigue.

Detailed Description: This is a multi-center, randomized, double-blind, placebo-controlled study to demonstrate the safety, tolerability, and effect of ACTH on fatigue in patients with relapsing multiple sclerosis (RMS). The primary objective of this study is to assess the efficacy of ACTH versus placebo in reducing fatigability in patients with RMS. Secondary objectives include assessment of the tolerability and safety of twice-weekly ACTH treatment vs. placebo and evaluation of ACTH on depression, sleepiness, and quality of life measures and correlations between these measures.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 8

Inclusion Criteria

Have documented diagnosis of Relapsing MS as defined by McDonald Criteria 2011 Revision for at least 6 months
Have been treated with interferon beta 1a or 1b, glatiramer acetate, fingolimod, dimethyl fumarate, or teriflunomide for at least 6 months, with reported adherence rate of at least 75%, at time of screening
Have an Kurtzke Expanded Disability Status Scale (EDSS) score of 0 to 4, inclusive
Have Modified Fatigue Impact Scale (MFIS) ≥ 38 or Functional Systems Scores (FSS) ≥ 36, Beck Depression Inventory-II (BDI-II) greater than or equal to 19, and Expanded Disability Status Scale (EDSS) greater than or equal to 9
Women of childbearing potential must employ proven methods to prevent pregnancy during the course of the trial
Able to understand the purpose and risks of the study
Must be willing to sign an inform consent
Must be willing to follow the protocol requirements
Subject must agree not to receive any live or live-attenuated vaccine during the trial

Exclusion Criteria

Have any of the contraindications for Acthar Gel as listed in the approved label, including sensitivity to proteins of porcine origin.
Had treatment of systemic or oral corticosteroids of any type in 90 days prior to baseline/randomization
Had a relapse or documented objective neurologic worsening in 90 days prior to baseline/randomization
Has concurrent neurological disease other than multiple sclerosis
History of sleep apnea
History (within 90 days) of nocturnal pain and / or nocturnal spasms that interferes with or disrupts sleep, or uncontrolled nocturnal restless leg syndrome
History of psychosis, bipolar disorder, mania/hypomania
History of coronary heart disease, congestive heart failure, chronic pulmonary disease, emphysema, anemia, bleeding disorder, gastrointestinal bleeding, intestinal ulcer, clinically significant cardiac arrhythmia, Type I or II diabetes, uncontrolled hypertension, seizure disorder, cardiac arrhythmia, immune deficiency disorder, HIV-AIDS, tuberculosis, or dysthyroidal state (patients with a history of hypothyroidism or hyperthyroidism, which has been corrected to physiological levels will not be excluded)
History of substance abuse, other than tobacco within the past 5 years or current alcohol dependence
Current use of cannabis, opiates, benzodiazepines, barbiturates, gabapentin, pregabalin, topiramate, divalproex sodium, carbamazepine, oxcarbazepine, or any gaba-ergic medications other than tizanidine or Baclofen, which are permitted for spasticity treatment
History of any malignant neoplasm except for past basal cell or squamous cell carcinoma of the skin, that has been successfully treated prior to the screening visit
History of psychosis or history of use of neuroleptics including, but not restricted to, haloperidol, chlorpromazine, aripiprazole, olanzapine, risperidone
History of suicide attempt, current suicidal thinking or is preparing for suicide
Current use of Amphetamines or methylphenidate
Current use of modafinil, or armodafinil
Current use of amantidine
The subject must have had a medication-free interval of:

a. 7 days for prior use of: i. methylphenidate, amphetamine or dextroamphetamine ii. modafinil or armodafinil iii. diphenhydramine, phenylephrine, loratadine iv. gabapentin, pregabalin, topiramate, valproate/divalproex v. oxcarbazepine vi. codeine, hydrocodone, oxycodone, diphenhydramine, phenylephrine, gabapentin, pregabalin, topiramate, valproate/divalproex, oxcarbazepine, codeine, hydrocodone, oxycodone b. 14 days for prior use of: i. desloratadine ii. Amantidine iii. alprazolam, lorazepam, morphine, hydromorphone, amantidine, alprazolam, lorazepam iv. morphine, hydromorphone c. 28 days for prior use of: i. clonazepam ii. cannabis or other cannabinoids d. 90 days for prior use of carbamazepine

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ACTH	ACTH	The study drug (ACTH 40 units) will be given subcutaneously twice weekly for 2 weeks. If the patient tolerates this dosage regimen, the dose will be increased to 80 units twice weekly. If the 80 unit dosage is not tolerated, the dosage will be reduced to 40 units twice weekly for the remainder of the 24 week participation. The weekly doses will be given 3 days apart, for example, on every Monday and Thursday or every Tuesday and Friday.
Placebo	Placebo	Placebo will be given subcutaneously twice weekly for 28 weeks.

Primary Outcome Measures

Name	Time	Method
Fatigue at 28 Weeks	28 weeks	Patient-reported levels of fatigue as measured by score on the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS) at 28 weeks. The full-length MFIS consists of 21 items. A higher score on the MFIS indicates a greater impact of fatigue on a patient's activities. The FSS is a 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle in patients with a variety of disorders. Higher scores on each scale indicate a greater severity of fatigue.

Secondary Outcome Measures

Name	Time	Method
Depression at 28 Weeks	28 weeks	Patient-reported depression as measured by the Beck Depression Inventory-II (BDI-II) at 28 weeks. The BDI-II is a 21-item self-report multiple-choice inventory used as an indicator of the severity of depression. A higher score indicates a greater severity of depression.
Sleepiness at 28 Weeks	28 weeks	Patient-reported daytime sleepiness as measure by the Epworth Sleepiness Scale (ESS) at 28 weeks. The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life, or their 'daytime sleepiness'.
Quality of Life at 28 Weeks	28 weeks	Patient-reported quality of life as measured by the 36-Item Short Form Health Survey (SF-36) at 28 weeks. The SF-36 is a 36-item, patient-reported survey of patient mental and physical health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability.

Trial Locations

Locations (5): North Central Neurology Associates, PC
🇺🇸
Cullman, Alabama, United States
Providence Medical Group - Medford Neurology
🇺🇸
Medford, Oregon, United States
Swedish Medical Center
🇺🇸
Seattle, Washington, United States
MultiCare Health System -- Institute for Research and Innovation
🇺🇸
Tacoma, Washington, United States
Providence St. Vincent Medical Center
🇺🇸
Portland, Oregon, United States