Adrenocorticotropic Hormone (ACTH) for Post-op Inflammation in Proliferative Vitreoretinopathy (PVR)

Adrenocorticotropic Hormone for Intraocular Inflammation in Post-operative Proliferative Vitreoretinopathy Patients

This is a pilot study to measure levels of albumin and inflammatory cytokines [including Transforming Growth Factor-Beta (TGF-β) and Interleukin-1 Beta (IL-1β)] in the aqueous humor of post-operative proliferative vitreoretinopathy patients receiving subcutaneous injections of H.P. Acthar®, an adrenocorticotropic hormone (ACTH) analog. The study will be conducted at the Wilmer Eye Institute, Johns Hopkins Hospital. A total of 15 patients will be enrolled and randomized 2:1 to H.P. Acthar® or standard of care. Treatment duration will be 8 weeks and study duration will be 12 weeks. There will be a total of 7 study visits (baseline, day of surgery, post-operative day 1, week 1, week 4, week 8, and week 12).

Subjects will self-administer subcutaneous injections of 80 units of H.P. Acthar® starting on post-operative day 1 for twice a week until week 8. Subjects in the control arm will be managed per the standard of care. Aqueous samples will be obtained at the onset of surgery, 1 day, 1 week and 8 weeks after surgery. Aqueous levels of albumin and inflammatory cytokines (including TGF-β and IL-1β) will be measured at each time point.

Study Overview

• Status: Completed
• Conditions: Proliferative Vitreoretinopathy
• Intervention / Treatment: Drug: Adrenocorticotropic Hormone

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Wilmer Eye Institute, Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Signed informed consent and authorization of use and disclosure of protected health information
• Patients undergoing surgery for retinal detachment due to PVR

Exclusion Criteria:

• Patients with poorly controlled diabetes mellitus (defined as HbA1C ≥ 8.0% on any anti-diabetic medications or insulin. If the patient is using any anti-diabetic medication/insulin, he becomes eligible if the medication is used continuously for >30 days)
• Patients with poorly controlled hypertension (defined as systolic blood pressure >180 mm Hg and/or diastolic blood pressure >100 mm Hg at rest with up to 3 anti-hypertensive medications. If a patient's initial measurement exceeds these values, a second reading may be taken 30 or more mins later. If the patient is using any anti-hypertensives, he becomes eligible if the medication is used continuously for >30 days)
• Patients with congestive heart failure
• Patients with scleroderma
• Patients with osteoporosis
• Patients with active systemic fungal infection
• Patients with active ocular herpes simplex
• Patients with prior or active bleeding peptic ulcer
• Pregnant patients or patients who wish to become pregnant during the course of the study (females of child-bearing age will be counselled to use contraception for the duration of the study)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: H.P. Acthar ®; Subjects will self-administer subcutaneous injections of 80 units of adrenocorticotropic hormone analog starting on post-operative day 1 for twice a week until week 8.	Drug: Adrenocorticotropic Hormone; Adrenocorticotropic hormone (ACTH) is a melanocortin peptide hormone that is normally produced in the pituitary gland and acts as a major regulator of adrenal cortex function. It stimulates the adrenal cortex to produce and secrete glucocorticoids. ACTH is available for clinical usage as an injectable gel (H.P. Acthar®).; Other Names: Repository Corticotropin Injection; H.P. Acthar Gel
No Intervention: Controls; Subjects will be managed per the standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mean aqueous levels of albumin in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	The levels of albumin in the aqueous humor are indicative of blood-retinal barrier breakdown and will be measured in mg/dl	Baseline, 1 day after surgery, 8 weeks after surgery
Change in mean aqueous levels of TGF-B in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	The levels of TGF-B in the aqueous humor are indicative of intraocular inflammation and will be measured in mg/dl	Baseline, 1 day after surgery, 8 weeks after surgery
Change in mean aqueous levels of interleukin-1B (IL-1B) in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	The levels of IL-1B in the aqueous humor are indicative of intraocular inflammation and will be measured in mg/dl	Baseline, 1 day after surgery, 8 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mean aqueous levels of albumin in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	The levels of albumin in the aqueous humor are indicative of blood-retinal barrier breakdown and will be measured in mg/dl	Baseline, 1 day after surgery, 1 week after surgery
Change in mean aqueous levels of TGF-B in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	The levels of TGF-B in the aqueous humor are indicative of intraocular inflammation and will be measured in mg/dl	Baseline, 1 day after surgery, 1 week after surgery
Change in mean aqueous levels of interleukin-1B (IL-1B) in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	The levels of IL-1B in the aqueous humor are indicative of intraocular inflammation and will be measured in mg/dl	Baseline, 1 day after surgery, 1 week after surgery
Change in mean grade of aqueous cell in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	Aqueous cell is a clinical indicator of blood-retinal barrier breakdown and intraocular inflammation. It is assessed on slit-lamp examination and is graded on a scale from 0 to 4+, with 0 meaning no aqueous cell and 4+ meaning severe aqueous cell	1 week, 4 weeks, 8 weeks and 12 weeks after surgery
Change in mean grade of flare in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	Flare is a clinical indicator of blood-retinal barrier breakdown and intraocular inflammation. It is assessed on slit-lamp examination and is graded on a scale from 0 to 4+ with 0 meaning no flare and 4+ means severe flare	1 week, 4 weeks, 8 weeks and 12 weeks after surgery
Change in best-corrected visual acuity as measured by Early Treatment of Diabetic Retinopathy Study (ETDRS) score in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	The ETDRS score is a standardized score to assess visual acuity used in clinical research. The score ranges from 0 to 100, with higher scores corresponding to better visual acuity (a score of 100 corresponding to a Snellen visual acuity of 20/10).	Baseline, 1 week, 4 weeks, 8 weeks and 12 weeks after surgery
Percentage of post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls who develop recurrent retinal detachment	Recurrent retinal detachment is a common complication of PVR. It will be diagnosed based on clinical exam and supporting information from diagnostic tests such as Optical Coherence Tomography.	12 weeks after surgery
Percentage of post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls who develop macular edema	Macular edema is a common complication of intraocular surgery. It will be diagnosed based on clinical exam and supporting information from diagnostic tests such as Optical Coherence Tomography.	12 weeks after surgery

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Peter A Campochiaro, MD, Wilmer Eye Institute, Johns Hopkins School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2019
• Primary Completion (Actual): July 7, 2023
• Study Completion (Actual): July 7, 2023

Study Registration Dates

• First Submitted: October 31, 2018
• First Submitted That Met QC Criteria: October 31, 2018
• First Posted (Actual): November 1, 2018

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: August 4, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Post-operative Intraocular Inflammation
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Retinal Diseases; Inflammation; Vitreoretinopathy, Proliferative; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones; Adrenocorticotropic Hormone; Melanocyte-Stimulating Hormones; beta-Endorphin
• Other Study ID Numbers: IRB00179012

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No