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

NCT02446886 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: 1405015090
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; MS; RRMS; SPMS; ACTH

Outcome Measures

Primary Outcomes (1)

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

  Baseline, 12 months

Secondary Outcomes (5)

• Physical Disability as Measured by EDSS

  12 months

• Change in T2 Lesion Volume

  12 months

• Cortical Volume

  12 Months

• Whole Brain Volume

  12 months

• Longitudinal Assessment of MWF

  12 months

Study Arms (2)

One Time Treatment

ACTIVE COMPARATOR

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®)

Monthly Treatments

EXPERIMENTAL

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®)

Interventions

Adrenocorticotropic hormone (ACTH) gel (H.P. Acthar®) DRUG

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.

Also known as: ACTH, H.P. Acthar®

Monthly Treatments; One Time Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Mallinckrodt: collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Adrenocorticotropic Hormone; Gels

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Research Coordinator
• Organization: Weill Cornell Medicine

liz4005@med.cornell.edu

6469625736

Study Officials

• Susan Gauthier, DO

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2015
• First Posted: May 18, 2015
• Study Start: June 1, 2016
• Primary Completion: March 1, 2020
• Study Completion: June 1, 2020
• Last Updated: January 22, 2021
• Results First Posted: January 22, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)