A Trial of Neuroprotection With ACTH in Acute Optic Neuritis

NCT01838174 | Terminated Phase 4

• 1 other identifier: 13-0388
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

We hypothesize that the novel melanocortin-mediated anti-inflammatory effects of ACTH will reduce axonal loss following ON by limiting inflammatory optic nerve injury. We will compare the effect of ACTH and intravenous methylprednisolone therapy on axonal injury following ON using OCT, a sensitive, reproducible and noninvasive tool to measure RNFL thickness. The primary outcome will be the average RNFL thickness at 6 months. Additional pre-specified statistical analyses will compare the difference in the mean RNFL thickness at 6 months in the affected eye between the IV methylprednisolone- and Acthar-treated groups, and the mean 6-month affected eye RNFL thicknesses adjusted for the baseline unaffected eye RNFL. The secondary outcome measure will examine the frequency of optic nerves with RNFL swelling between the IV methylprednisolone- and Acthar-treated groups at 1 and 3 months. A predefined exploratory outcome will compare the ganglion cell plus inner plexiform layer (GC+IPL) thickness at 6 months between treatment groups. Additional tertiary outcome will be the assessment of changes in fatigue, mood, visual function depression, and quality of life in patients with AON. Assessment will be completed by administration of the following questionnaires: Modified Fatigue Impact Scale, Multiple Sclerosis Quality of Life 54 Instrument, 25-item Visual Function Questionnaire with 10-item supplement, Beck's Depression Inventory. These questionnaires have been validated for the MS (AON) population. Descriptive and correlative analysis will be done at each visit time point to assess for QOL for this study population.

Conditions

Multiple Sclerosis

Keywords

Optic Neuritis

Outcome Measures

Primary Outcomes (1)

• Retinal Nerve Fiber Layer (RNFL) thickness

  The primary outcome will be the average RNFL thickness at 6 months.

  6 months

Secondary Outcomes (1)

• Frequency of RNFL swelling

  1 and 3 months

Other Outcomes (5)

• Comparison of ganglion cell plus inner plexiform layer (GC+IPL) thickness at 6 months

  6 months

• Assessment of changes in fatigue in patients with AON.

  Baseline, Month 1, 3, 6

• Assessment in mood in patients with AON.

  Baseline, Month 1, 3, 6

Study Arms (2)

Acthar Gel (ACTH)

EXPERIMENTAL

15 days of intramuscular (IM) or sub-cutaneous corticotropin (SQ) Acthar (ACTH).

Drug: ACTHAR Gel (ACTH)

IV methylprednisolone (steroids)

ACTIVE COMPARATOR

3 days of IV methylprednisolone (steroids) followed by 11 days of oral prednisone

Drug: IV methylprednisolone (steroids)

Interventions

ACTHAR Gel (ACTH) DRUG

15 days of daily injections

Also known as: ACTH

Acthar Gel (ACTH)

IV methylprednisolone (steroids) DRUG

3 days of intravenous methylprednisolone followed by 11 days of oral taper

Also known as: methylprednisolone

IV methylprednisolone (steroids)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Ability to provide written informed consent before any study assessment is performed.
• Male and female patients aged between 18 and 55 years, inclusive.
• Diagnosis of clinically unilateral acute demyelinating optic neuritis (ADON)
• Clinical signs and symptoms of ADON starting within the 14 day prior to intended randomization (loss of vision, pain on movement, impairment of color vision).
• The qualifying episode of optic neuritis must be the first clinical episode of optic neuritis in the affected eye.
• Able to undergo treatment with intravenous methylprednisolone or Acthar gel.

You may not qualify if:

• Functionally or clinically relevant comorbidity of the affected eye (e.g., glaucoma, amblyopia, optic nerve hypoplasia, macular hole, macular edema, vitreomacular traction, uveitis, diabetes, optic neuritis, or other diseases of the optic nerve or a history thereof).
• Bilateral optic neuritis.
• Concurrent functionally or clinically relevant disturbances of the eye not affected by ADON.
• High clinical likelihood of a form of optic neuritis other than ADON (e.g., no pain on movement, no light perception, severe optic disk edema, atrophic optic disk, retinal exudates, or hemorrhages).
• Non-assessable OCT at screening.
• Refractive error greater than ±5 diopters or (pre-surgical value to be used for patients having undergone refractive surgery).
• Patients with an immune system disorder other than MS or ADON (e.g. rheumatoid arthritis, scleroderma, Sjogren's syndrome, Crohn's disease, ulcerative colitis, etc.) or with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug-induced immune deficiency). Diagnosis of neuromyelitis optica or MOG-IgG will not exclude a patient from the study but will be accounted for in the data analysis.
• Prior treatment with IVMP or Acthar gel within the past 30 days.
• Treatment with, mitoxantrone, cyclophosphamide, mycophenolate, azathioprine, or other non-approved agents for the treatment of relapsing forms of MS.
• Concurrent use of 4-aminopyridine.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Mallinckrodt: collaborator
• University of Pennsylvania: collaborator

Study Sites (2)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

University of Pennsylvania Scheie Eye Institute

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Bennett JL, Grove NC, Johnson RK, Mizenko C, DuPont JC, Wagner BD, Lynch AM, Frohman TC, Shindler KS, Frohman EM. A Randomized Prospective Trial Comparing Repository Corticotropin Injection and Intravenous Methylprednisolone for Neuroprotection in Acute Optic Neuritis. J Neuroophthalmol. 2023 Sep 1;43(3):323-329. doi: 10.1097/WNO.0000000000001878. Epub 2023 Jun 1.

  PMID: 37261907 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Optic Neuritis

Interventions

Adrenocorticotropic Hormone; Methylprednisolone; Steroids

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Eye 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; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Jeffrey Bennett, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• Kenneth Shindler, MD, PhD

  University of Pennsylvania Scheie Eye Institute

  PRINCIPAL INVESTIGATOR

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: April 18, 2013
• First Posted: April 23, 2013
• Study Start: May 1, 2013
• Primary Completion: January 13, 2022
• Study Completion: January 13, 2022
• Last Updated: April 27, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)