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Trial · Interventional

TerminatedPhase 4Results postedRegistry data

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

NCTNCT02446886 (opens ClinicalTrials.gov in a new tab)Other id1405015090
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Terminated
Phase
Phase 4
Enrollment
15 participants (actual)
Sponsor
Weill Medical College of Cornell University · Other
Design
Randomized · Open label (no masking)
Countries
1 country

United States

Start
Jun 2016
Primary completion
Mar 2020
Completion
Jun 2020
First posted
18 May 2015 (estimated)
Last update posted
22 Jan 2021
Conditions
Multiple Sclerosis

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201620172018201920202021
  1. Ph 4

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

    NCT02446886

    Jun 2016 to Jun 2020

    Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

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

Arms2

  • 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.)

  • 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.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change in Myelin Water Fraction (MWF) Within New Enhancing Lesions Over the Course of 12 Months

    Time frame · Baseline, 12 months

    Registry description

    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 outcomes(5)

  1. Physical Disability as Measured by EDSS

    Time frame · 12 months

    Registry description

    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

    Registry description

    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

    Registry description

    Change in cortical volume of the brain over 12 months.

  4. Whole Brain Volume

    Time frame · 12 months

    Registry description

    Change in whole brain volume over 12 months.

  5. Longitudinal Assessment of MWF

    Time frame · 12 months

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Baseline, 12 months

Change in Myelin Water Fraction (MWF) Within New Enhancing Lesions Over the Course of 12 Months

GroupValue (myelin water fraction)Spread
One Time Treatment1.71.8
Monthly Treatments-0.201.3
Secondary and other outcome results(5)
Secondary outcomeMean· 12 months

Physical Disability as Measured by EDSS

GroupValue (score on a scale)Spread
One Time Treatment.5.9
Monthly Treatments1.11.5
Secondary outcomeMean· 12 months

Change in T2 Lesion Volume

GroupValue (millimeters cubed)Spread
One Time Treatment683.591241.92
Monthly Treatments1092.081513.45
Secondary outcome· 12 Months

Cortical Volume

GroupValue
One Time Treatmentnot posted
Monthly Treatmentsnot posted
Secondary outcome· 12 months

Whole Brain Volume

GroupValue
One Time Treatmentnot posted
Monthly Treatmentsnot posted
Secondary outcomeMean· 12 months

Longitudinal Assessment of MWF

GroupValue (myelin water fraction)Spread
One Time Treatment1.71.8
Monthly Treatments-.21.3

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
One Time TreatmentMS 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.) 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.0 / 80 / 80 / 8
Monthly TreatmentsIntervention 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. 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 recep0 / 70 / 70 / 7

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Accepted
Inclusion and exclusion criteria, as posted
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

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