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

Study Overview
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Brief Summary
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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.

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

Conditions
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Proliferative Vitreoretinopathy

Intervention / Treatment
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* Drug: Adrenocorticotropic Hormone


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: H.P. Acthar ®<br>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<br>* 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®).<br>* Other names: Repository Corticotropin Injection;|
| No Intervention: Controls<br>Subjects will be managed per the standard of care. | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-operative Intraocular Inflammation