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

Early Phase 1

Completed

• Conditions: Proliferative Vitreoretinopathy
• Interventions: Drug: Adrenocorticotropic Hormone

• Registration Number: NCT03727776
• Lead Sponsor: Johns Hopkins University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-10-31
• Study First Submitted QC: 2018-10-31
• Study First Posted: 2018-11-01
• Study Start: 2019-08-19
• Primary Completion: 2023-07-07
• Study Completion: 2023-07-07
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-04
• Last Update Posted: 2023-08-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
H.P. Acthar ®	Adrenocorticotropic Hormone	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	Baseline, 1 week, 4 weeks, 8 weeks and 12 weeks after surgery	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).
Change in mean aqueous levels of TGF-B in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	Baseline, 1 day after surgery, 1 week after surgery	The levels of TGF-B in the aqueous humor are indicative of intraocular inflammation and will be measured in mg/dl
Change in mean aqueous levels of interleukin-1B (IL-1B) in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	Baseline, 1 day after surgery, 1 week after surgery	The levels of IL-1B in the aqueous humor are indicative of intraocular inflammation and will be measured in mg/dl
Change in mean grade of flare in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	1 week, 4 weeks, 8 weeks and 12 weeks after surgery	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
Change in mean grade of aqueous cell in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	1 week, 4 weeks, 8 weeks and 12 weeks after surgery	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
Percentage of post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls who develop recurrent retinal detachment	12 weeks after surgery	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.
Percentage of post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls who develop macular edema	12 weeks after surgery	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.
Change in mean aqueous levels of albumin in post-operative PVR patients receiving subcutaneous injections of H.P. Acthar® versus controls	Baseline, 1 day after surgery, 1 week after surgery	The levels of albumin in the aqueous humor are indicative of blood-retinal barrier breakdown and will be measured in mg/dl

Trial Locations

Locations (1)

Wilmer Eye Institute, Johns Hopkins Hospital; 🇺🇸 Baltimore, Maryland, United States