Ignite Creation Date:
2024-05-06 @ 9:46 AM
Last Modification Date:
2024-10-26 @ 12:19 PM
Study NCT ID:
NCT03063021
Status:
COMPLETED
Last Update Posted:
2022-09-19
First Post:
2017-02-16
Brief Title:
The FIGHT-RP1 Study
Sponsor:
Johns Hopkins University
Organization:
Johns Hopkins University
Study Overview
Official Title:
A Phase 1 Open Label Dose Ranging Study to Assess the Safety and Tolerability of N-Acetylcysteine NAC in Patients With Retinitis Pigmentosa FIGHT-RP1 Study
Status:
COMPLETED
Status Verified Date:
2021-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FIGHT-RP1
Brief Summary:
Retinitis Pigmentosa RP is a devastating eye disease and at present there are no known treatment options that can alter the rate of vision loss In a series of studies in animal models the effects of exposing cones in the periphery of the retina to a large excess of oxygen results in progressive oxidative damage to cone photoreceptors and cone cell death Compared to control patients those with RP showed significant reduction in the reduced to oxidized glutathione ratio GSHGSSG in aqueous humor and a significant increase in protein carbonyl content This demonstration of oxidative stress and oxidative damage in the eyes of patients with RP suggests that oxidative damage-induced cone cell death in animal models of RP may translate to humans with RP and support the hypotheses that 1 potent antioxidants will promote cone survival and function in patients with RP and 2 aqueous GSHGSSG ratio and carbonyl content on proteins provide useful biomarkers of disease activity in this patient population Orally administered N-Acetylcysteine NAC has been found to be a particularly effective antioxidant that promotes prolonged cone survival and maintenance of cone function in a mouse model of RP There is good rationale to test the effect of NAC in patients with RP The first step is to test different dosing regimens to identify the lowest dose that is able to restore aqueous GSHGSSG ratio and reduce carbonyl adducts on aqueous proteins
In patients with Idiopathic Pulmonary Fibrosis polymorphisms within the TOLLIP gene were found to influence outcomes of NAC-treated patients The product of the TOLLIP gene toll-interacting protein is an inhibitory adaptor protein downstream of toll-like receptors mediators of innate and adaptive immunity The identification of the influence of TOLLIP polymorphisms on the effect of NAC in Idiopathic Pulmonary Fibrosis provides the rationale for collecting DNA and genotyping the same single nucleotide polymorphisms SNPs in the current trial In addition to this candidate gene genetic analysis patient RNA will be collected and banked for future transcriptome analysis The rationale for this is to identify gene expression changes that modify disease progression in RP There is substantial variability in the rate of progression among patients with RP A patient who loses all vision early in life can have a sibling with the same mutation who maintains vision into advanced age This suggests that modifier genes can have a major impact on cone survival This study will test the hypothesis that the level of expression of gene products that contribute to the antioxidant defense system may influence cone cell death and hence the rate of loss of visual field It is also possible that gene expression differences may contribute to differences in response to NAC For these reasons collecting RNA samples from patients will allow next-generation sequencing in the future to understand the transcriptome background on which the study intervention has been performed
In patients with Idiopathic Pulmonary Fibrosis polymorphisms within the TOLLIP gene were found to influence outcomes of NAC-treated patients The product of the TOLLIP gene toll-interacting protein is an inhibitory adaptor protein downstream of toll-like receptors mediators of innate and adaptive immunity The identification of the influence of TOLLIP polymorphisms on the effect of NAC in Idiopathic Pulmonary Fibrosis provides the rationale for collecting DNA and genotyping the same single nucleotide polymorphisms SNPs in the current trial In addition to this candidate gene genetic analysis patient RNA will be collected and banked for future transcriptome analysis The rationale for this is to identify gene expression changes that modify disease progression in RP There is substantial variability in the rate of progression among patients with RP A patient who loses all vision early in life can have a sibling with the same mutation who maintains vision into advanced age This suggests that modifier genes can have a major impact on cone survival This study will test the hypothesis that the level of expression of gene products that contribute to the antioxidant defense system may influence cone cell death and hence the rate of loss of visual field It is also possible that gene expression differences may contribute to differences in response to NAC For these reasons collecting RNA samples from patients will allow next-generation sequencing in the future to understand the transcriptome background on which the study intervention has been performed
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None