Proliferative Vitreoretinopathy
Conditions
Keywords
Post-operative Intraocular Inflammation
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.
Interventions
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®).
Sponsors
Mallinckrodt
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 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 |
| 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 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 |
Countries
United States
Outcome results
None listed