ACTH for Fatigue in Multiple Sclerosis Patients

• Sponsor: Providence Health & Services (Other)
• Overall Status: Completed
• CT.gov ID: NCT02315872
• Collaborator: Mallinckrodt (Industry)
• Enrollment: 8
• Locations: 5
• Arms: 2
• Actual Duration (Months): 42.7
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis, Relapsing-Remitting	Drug: ACTH; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effect of ACTH (Acthar) on Measures of Chronic Fatigue in Patients With Relapsing Multiple Sclerosis.
• Actual Study Start Date: May 22, 2015
• Actual Primary Completion Date: Jun 20, 2017
• Actual Study Completion Date: Dec 13, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: ACTH; ACTH injections twice weekly for 28 weeks.; Other Names: Acthar Gel Repository Corticotropin Injection
Placebo Comparator: Placebo Placebo will be given subcutaneously twice weekly for 28 weeks.	Drug: Placebo; Placebo injections twice weekly for 28 weeks.; Other Names: Control

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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'.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. 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
2. 28 days for prior use of: i. clonazepam ii. cannabis or other cannabinoids d. 90 days for prior use of carbamazepine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	North Central Neurology Associates, PC	Cullman	Alabama	United States	35058
2	Providence Medical Group - Medford Neurology	Medford	Oregon	United States	97504
3	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
4	Swedish Medical Center	Seattle	Washington	United States	98122
5	MultiCare Health System -- Institute for Research and Innovation	Tacoma	Washington	United States	98405

Sponsors and Collaborators

• Providence Health & Services
• Mallinckrodt

Investigators

• Principal Investigator: Stanely Cohan, MD, PhD, Providence Health & Services

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 30, 2015

More Information

Additional Information:

• Providence Health & Services Brain and Spine Institute

Publications

None provided.

• Responsible Party: Providence Health & Services
• ClinicalTrials.gov Identifier: NCT02315872
• Other Study ID Numbers: 13-120A
• First Posted: Dec 12, 2014
• Last Update Posted: Sep 9, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Providence Health & Services: Multiple Sclerosis; Acthar Gel; ACTH; Fatigue
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Fatigue; Adrenocorticotropic Hormone

Study Results

Participant Flow

Arm/Group Title	ACTH	Placebo
Arm/Group Description	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. ACTH: ACTH injections twice weekly for 28 weeks.	Placebo will be given subcutaneously twice weekly for 28 weeks. Placebo: Placebo injections twice weekly for 28 weeks.
Period Title: Overall Study
STARTED	4	4
COMPLETED	1	3
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	ACTH	Placebo	Total
Arm/Group Description	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. ACTH: ACTH injections twice weekly for 28 weeks.	Placebo will be given subcutaneously twice weekly for 28 weeks. Placebo: Placebo injections twice weekly for 28 weeks.	Total of all reporting groups
Overall Participants	4	4	8
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 100%	3 75%	7 87.5%
>=65 years	0 0%	1 25%	1 12.5%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	54.5	52	53.25
Sex: Female, Male (Count of Participants)
Female	1 25%	4 100%	5 62.5%
Male	3 75%	0 0%	3 37.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 25%	0 0%	1 12.5%
White	3 75%	4 100%	7 87.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%	4 100%	8 100%
Modified Fatigue Impact Scale (MFIS) (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	47.75	48.5	48.125
Fatigue Severity Scale (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	53.25	44.5	48.875
Beck Depression Inventory-II (BDI-II) (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	13	9.75	11.375
The Epworth Sleepiness Scale (ESS) (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	7	10.75	8.875
Short Form (36) Health Survey (SF-36) Mental Score (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	43	47.5	45.25
SF-36 Physical Score (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	37.75	45	41.25

Outcome Measures

1. Primary Outcome

Title	Fatigue at 28 Weeks
Description	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.
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ACTH	Placebo
Arm/Group Description	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. ACTH: ACTH injections twice weekly for 28 weeks.	Placebo will be given subcutaneously twice weekly for 28 weeks. Placebo: Placebo injections twice weekly for 28 weeks.
Measure Participants	4	4
MFIS	56.50	29.00
FSS	55.00	40.00

2. Secondary Outcome

Title	Depression at 28 Weeks
Description	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.
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ACTH	Placebo
Arm/Group Description	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. ACTH: ACTH injections twice weekly for 28 weeks.	Placebo will be given subcutaneously twice weekly for 28 weeks. Placebo: Placebo injections twice weekly for 28 weeks.
Measure Participants	4	4
Median (Full Range) [score on a scale]	16.50	40.00

3. Secondary Outcome

Title	Sleepiness at 28 Weeks
Description	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'.
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ACTH	Placebo
Arm/Group Description	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. ACTH: ACTH injections twice weekly for 28 weeks.	Placebo will be given subcutaneously twice weekly for 28 weeks. Placebo: Placebo injections twice weekly for 28 weeks.
Measure Participants	4	4
Median (Full Range) [score on a scale]	11.00	7.00

4. Secondary Outcome

Title	Quality of Life at 28 Weeks
Description	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.
Time Frame	28 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ACTH	Placebo
Arm/Group Description	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. ACTH: ACTH injections twice weekly for 28 weeks.	Placebo will be given subcutaneously twice weekly for 28 weeks. Placebo: Placebo injections twice weekly for 28 weeks.
Measure Participants	4	4
SF-36 Mental	39.50	49.00
SF-36 Physical	37.50	45.00

Adverse Events

Time Frame	Data was collected over 28 weeks.
Arm/Group Title	ACTH		Placebo
Arm/Group Description	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. ACTH: ACTH injections twice weekly for 28 weeks.		Placebo will be given subcutaneously twice weekly for 28 weeks. Placebo: Placebo injections twice weekly for 28 weeks.
All Cause Mortality
	ACTH		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)
Serious Adverse Events
	ACTH		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	ACTH		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		3/4 (75%)
Cardiac disorders
systolic aortic murmur	1/4 (25%)	1	0/4 (0%)	0
hypertension	1/4 (25%)	1	0/4 (0%)	0
Eye disorders
worsening vision	0/4 (0%)	0	1/4 (25%)	1
Gastrointestinal disorders
incontinence	0/4 (0%)	0	1/4 (25%)	1
heartburn	0/4 (0%)	0	1/4 (25%)	1
dysphagia	1/4 (25%)	1	0/4 (0%)	0
appendicitis	1/4 (25%)	1	0/4 (0%)	0
colonic diverticula	1/4 (25%)	1	0/4 (0%)	0
General disorders
insomnia	1/4 (25%)	1	1/4 (25%)	1
agitation	1/4 (25%)	1	0/4 (0%)	0
anxiety	1/4 (25%)	1	0/4 (0%)	0
depression	1/4 (25%)	1	1/4 (25%)	1
fatigue	1/4 (25%)	1	0/4 (0%)	0
confusion	1/4 (25%)	1	0/4 (0%)	0
memory loss	1/4 (25%)	1	0/4 (0%)	0
irritability	1/4 (25%)	1	0/4 (0%)	0
pain	0/4 (0%)	0	1/4 (25%)	5
weight gain	0/4 (0%)	0	1/4 (25%)	1
weakness	1/4 (25%)	1	1/4 (25%)	1
loss of coordination	0/4 (0%)	0	1/4 (25%)	1
weight gain	2/4 (50%)	2	0/4 (0%)	0
Headache	1/4 (25%)	1	0/4 (0%)	0
edema	1/4 (25%)	1	0/4 (0%)	0
diaphoresis	1/4 (25%)	1	0/4 (0%)	0
syncope	1/4 (25%)	1	0/4 (0%)	0
pain and numbness	0/4 (0%)	0	1/4 (25%)	1
Infections and infestations
bronchitis	1/4 (25%)	1	1/4 (25%)	1
Sinus infection	1/4 (25%)	1	1/4 (25%)	1
Flu	2/4 (50%)	2	0/4 (0%)	0
Herpes simplex	1/4 (25%)	1	0/4 (0%)	0
Yeast infection	0/4 (0%)	0	1/4 (25%)	1
Musculoskeletal and connective tissue disorders
Worsening muscle spasticity	0/4 (0%)	0	1/4 (25%)	1
Broken toe	1/4 (25%)	1	0/4 (0%)	0
Renal and urinary disorders
enlarged prostate	1/4 (25%)	1	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
worsening asthma	0/4 (0%)	0	1/4 (25%)	2
Skin and subcutaneous tissue disorders
injection site reaction	1/4 (25%)	2	2/4 (50%)	3
decreased cutaneous sensation	1/4 (25%)	1	0/4 (0%)	0
plantar dysthesia	1/4 (25%)	1	0/4 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.