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Adrenocorticotropic Hormone (ACTH) Effects on Myelination in Subjects With MS

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ClinicalTrials.gov Identifier: NCT02446886
Recruitment Status : Terminated (Slow enrollment)
First Posted : May 18, 2015
Results First Posted : January 22, 2021
Last Update Posted : January 22, 2021
Sponsor:
Collaborator:
Mallinckrodt
Information provided by (Responsible Party):
Weill Medical College of Cornell University

Brief Summary:

The primary objective of this study is to determine if monthly pulse doses of a three-day course ACTH (H.P. Acthar®) is more effective at recovering myelin at 12 months, as measured by myelin water fraction (MWF), in new multiple sclerosis lesions as compared to one course of treatment.

The main secondary objective is to utilize every three month MWF measurements to determine the peak time of remyelination in new multiple sclerosis lesions when followed over the course of 12 months.


Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: Adrenocorticotropic hormone (ACTH) gel (H.P. Acthar®) Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adrenocorticotropic Hormone (ACTH) Effects on Myelination in Subjects With MS
Actual Study Start Date : June 2016
Actual Primary Completion Date : March 2020
Actual Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: One Time Treatment

MS patients enrolled in this study will be randomized into:

Intervention for Group A: 80 units/day ACTH (H.P. Acthar®)for 3-5 days (The dose could be adjusted based on the individual needs of the patients up to 80-120 units daily for 2-3 weeks.)

Drug: Adrenocorticotropic hormone (ACTH) gel (H.P. Acthar®)

Adrenocorticotropic hormone (ACTH) gel, a long-acting formulation of the full sequence ACTH that includes other pro-opiomelanocortin (POMC) peptides, is considered an alternative to corticosteroids in the treatment of relapses (currently FDA approved for this indication).

ACTH (H.P. Acthar®) gel exerts direct anti-inflammatory and immune-modulating effects within the CNS, specifically on infiltrating macrophages and resident microglia as well as protecting mature oligodendrocytes from inflammation-related damage and excitotoxicity. These effects are mediated not only via induction of endogenous corticosteroid production but also via effects on melanocortin receptors.

Other Names:
  • ACTH
  • H.P. Acthar®

Experimental: Monthly Treatments
Intervention for Group B: 80 units/day ACTH (H.P. Acthar®) for 3-5 days (The dose could be adjusted based on the individual needs of the patients up to 80-120 units daily for 2-3 weeks.), followed by monthly 80 units/day ACTH for 3 days for 12 months of treatment.
Drug: Adrenocorticotropic hormone (ACTH) gel (H.P. Acthar®)

Adrenocorticotropic hormone (ACTH) gel, a long-acting formulation of the full sequence ACTH that includes other pro-opiomelanocortin (POMC) peptides, is considered an alternative to corticosteroids in the treatment of relapses (currently FDA approved for this indication).

ACTH (H.P. Acthar®) gel exerts direct anti-inflammatory and immune-modulating effects within the CNS, specifically on infiltrating macrophages and resident microglia as well as protecting mature oligodendrocytes from inflammation-related damage and excitotoxicity. These effects are mediated not only via induction of endogenous corticosteroid production but also via effects on melanocortin receptors.

Other Names:
  • ACTH
  • H.P. Acthar®




Primary Outcome Measures :
  1. Change in Myelin Water Fraction (MWF) Within New Enhancing Lesions Over the Course of 12 Months [ Time Frame: Baseline, 12 months ]

    Primary outcome: The absolute change in lesion MWF (over our test-retest variability) between baseline and one year MRI's will be calculated and compared between treatment groups.

    Method to assess lesion MWF: FAST-T2 is a multi-compartment T2 relaxometry MRI technique wherein the contribution of water associated with myelin and other tissue compartments is differentiated using T2 decay curve analysis. The relative contribution of the myelin water with respect to total water is represented as MWF. A higher MWF within a lesion reflects higher myelin content within that lesion.

    For this analysis, MWF maps were reconstructed from FAST-T2 MRI data by using a multi-voxel nonlinear least-squares data-fitting algorithm with spatial smoothness constraints. MWF was calculated as the ratio of the myelin water signal to the total water signal within a voxel. Lesion MWF is an average of the voxels present within an individual lesion.



Secondary Outcome Measures :
  1. Physical Disability as Measured by EDSS [ Time Frame: 12 months ]

    Expanded Disability Status Scale (EDSS)

    0 Normal neurological exam, no disability in any FS 1.0 No disability, minimal signs in one FS 1.5 No disability, minimal signs in more than one FS 2.0 Minimal disability in one FS 2.5 Mild disability in one FS or minimal disability in two FS 3.0 Moderate disability in one FS, or mild disability in three or four FS. No impairment to walking 3.5 Moderate disability in one FS and more than minimal disability in several others. No impairment to walking 4.0 Significant disability but self-sufficient and up and about some 12 hours a day. Able to walk without aid or rest for 500m 4.5 Significant disability but up and about much of the day, able to work a full day, may otherwise have some limitation of full activity or require minimal assistance. Able to walk without aid or rest for 300m

    10.0 Death due to MS

    A higher score means a worse outcome.


  2. Change in T2 Lesion Volume [ Time Frame: 12 months ]
    The change in T2 lesion volume between baseline and one year MRI's will be calculated and compared between treatment groups.

  3. Cortical Volume [ Time Frame: 12 Months ]
    Change in cortical volume of the brain over 12 months.

  4. Whole Brain Volume [ Time Frame: 12 months ]
    Change in whole brain volume over 12 months.

  5. Longitudinal Assessment of MWF [ Time Frame: 12 months ]

    Outcome measure: Longitudinal assessment of MWF (every 3 months) to determine the dynamics of myelin change over 12 months.

    Method to assess lesion MWF: FAST-T2 is a multi-compartment T2 relaxometry MRI technique wherein the contribution of water associated with myelin and other tissue compartments is differentiated using T2 decay curve analysis. The relative contribution of the myelin water with respect to total water is represented as MWF. A higher MWF within a lesion reflects higher myelin content within that lesion.

    For this analysis, MWF maps were reconstructed from FAST-T2 MRI data by using a multi-voxel nonlinear least-squares data-fitting algorithm with spatial smoothness constraints. MWF was calculated as the ratio of the myelin water signal to the total water signal within a voxel. Lesion MWF is an average of the voxels present within an individual lesion.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patients with RRMS or SPMS with new contrast-enhancing lesions who will start as part of their standard of care ACTH.

Exclusion Criteria:

  • Patients having received oral or IV corticosteroids within one month prior to initial scan demonstrating contrast enhancing lesion
  • Patients with known or new allergy to ACTH
  • Patients being treated with Natalizumab, Rituximab, and Cyclophosphamide
  • Patients unwilling to have serial MRI exams
  • Patients unable to undergo MRI imaging because of having an artificial heart valve, metal plate, pin, or other metallic objects in their body or is unable to complete all the MRI scans required for this study
  • Patients with acute or chronic renal disease in whom administration of gadolinium may pose risk of nephrogenic systemic fibrosis
  • Patients that are pregnant
  • Premenopausal woman not willing to use at least one form of contraception
  • Patients with a known history of diabetes mellitus
  • Patients with a known history of osteoporosis or bone density values in the osteoporosis range at screening
  • Progressive neurological disorder other than RRMS or SPMS
  • Clinically significant cardiovascular disease, including myocardial infarct within last 6 months, unstable ischemic heart disease, congestive heart failure, or angina
  • Subjects on chronic steroid therapy for treatment of MS or other systematic disease
  • Subject currently has a significant medical condition (other than MS) including the following: neurological, psychiatric, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular (including uncontrolled hypertension), gastrointestinal, urological disorder, or central nervous system (CNS) infection that would pose a risk to the subject if they were to participate in the study or that might confound the results of the study

    o Note: Active medical conditions that are minor or well-controlled are not exclusionary if, in the judgment of the Primary Investigator, they do not affect risk or the subject or the study results.

  • Subject is unable to cooperate with any study procedures, unlikely to adhere to the study procedures and keep appointments, in the opinion of the Investigator, or was planning to relocate during the study

Information from the National Library of Medicine

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): NCT02446886


Locations
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United States, New York
Weill Cornell Medicine
New York, New York, United States, 10021
Sponsors and Collaborators
Weill Medical College of Cornell University
Mallinckrodt
Investigators
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Principal Investigator: Susan Gauthier, DO Weill Medical College of Cornell University
  Study Documents (Full-Text)

Documents provided by Weill Medical College of Cornell University:
Study Protocol  [PDF] October 13, 2015
No Statistical Analysis Plan (SAP) exists for this study.

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Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT02446886    
Other Study ID Numbers: 1405015090
First Posted: May 18, 2015    Key Record Dates
Results First Posted: January 22, 2021
Last Update Posted: January 22, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Weill Medical College of Cornell University:
Multiple Sclerosis
MS
RRMS
SPMS
ACTH
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Adrenocorticotropic Hormone
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Hormones
Melanocyte-Stimulating Hormones
beta-Endorphin
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action