Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa

Retinitis Pigmentosa Clinical Trial

Official title:

Effects of Oral N- Acetylcysteine on Macular Function in Retinitis Pigmentosa; a Phase 2 Randomized Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04864496
• Other study ID #: 1400
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 17, 2021
• Est. completion date: December 20, 2022

Study information

• Verified date: April 2021
• Source: Shahid Beheshti University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Retinitis pigmentosa (RP) is an inherited retinal disease with great heterogeneity. RP comprises a large group of genetic disorders causing progressive loss of vision. Despite many suggested treatments, there is actually no effective therapy for most types of RP at present. Mutations that cause RP initially lead to rod cell death. After rod photoreceptors' death, cone photoreceptors also gradually die. There are several hypotheses as to why mutation-induced rod photoreceptor cell death invariably leads to gradual dysfunction and death of cone photoreceptors resulting in severe visual acuity loss and blindness. Rods constitute 95 percent of cells in the outer retina. As they degenerate, oxygen consumption is reduced and the level of tissue oxygen markedly increases. After rods degeneration, several markers of oxidative damage appear in cones. This oxidative stress over time may lead to cone dysfunction and death. Antioxidants reduce markers of oxidative damage and promote cone function and survival. In RP, cone death occurs as a result of the death of rods, rather than as the result of the pathogenic mutations and therefore treatment with antioxidants may have the potential to be applied to all patients with RP irrespective of the disease-causing mutation.

N-acetylcysteine is a derivative of L cysteine that plays a role in the biosynthesis of glutathione and neutralizes reactive oxygen species. It also has a direct antioxidant activity via its reactive sulfhydryl agent. Its systemic use shows an acceptable safety profile. It has been shown that the use of systemic N-acetylcysteine provides significant intraocular concentration and antioxidant activity that may lead to the promotion of cone function and survival.

In a recent phase 1 randomized clinical trial (RCT), it was revealed that oral N-acetylcysteine (NAC) was safe and well-tolerated in patients with moderately advanced RP and might improve sub-optimally functioning macular cones. The authors concluded that a randomized, placebo-controlled trial is needed to determine if oral NAC can provide long-term stabilization and/or improvement in visual function in patients with RP. In this phase 2 RCT, eligible patients with the diagnosis of moderately advanced RP are randomly divided into two groups; treatment group (N-acetylcysteine tablets) and controls (placebo). Each group will be treated for 6 months. In this study, we will investigate if the use of oral N- acetylcysteine as a potent antioxidant agent can slow down or reverse the disease process in RP patients with prior moderate loss of vision. It may potentially demonstrate a treatment modality regardless of the genetic type of RP. The primary outcome measure will be the stability or improvement of the best-corrected visual acuity (BCVA). The secondary outcome measures will be changes in color vision, electroretinogram, visual field, structural OCT indices after 6 months. The same parameters will be re-evaluated 3 months after discontinuation of treatment at month 9.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: December 20, 2022
• Est. primary completion date: March 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• RP patients with the best-corrected visual acuity (BCVA) between 20/30 and 20/120.

Exclusion Criteria:

• Patients with other types of retinal dystrophy

• Systemic or syndromic RP

• RP patients with cystoid macular edema (CME) and the presence of cystoid changes in the foveal area

• RP patients with other concomitant ocular diseases

• RP patients with a history of any ocular surgery or intravitreal injection within 6 months before the study enrollment

• RP patients who have received any supplemental drugs during the past three months before the study enrollment

Related Conditions & MeSH terms

• Retinitis
• Retinitis Pigmentosa

Intervention

Drug:
• Prescribe N-acetylcysteine tablets
N-acetylcysteine tablets ,1200 mg two times daily
• Prescribe placebo tablets
manufactured by Daroo Salamat Pharmed, two times daily

Locations

Country	Name	City	State
Iran, Islamic Republic of	Ophthalmic Research Center	Tehran

Sponsors (1)

Lead Sponsor	Collaborator
Shahid Beheshti University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change of the best corrected visual acuity (BCVA) from baseline to month 6	ETDRS chart	6 months
Secondary	Change of the ellipsoid zone (EZ) width from baseline to month 6	spectral domain optical coherence tomography (SD-OCT)	6 months
Secondary	Changes of the wave amplitude of the flicker response from baseline to month 6	Full field electroretinograph (ffERG) testing	6 months
Secondary	Change of the foveal and macular sensitivity from baseline to month 6	visual field testing	6 months
Secondary	Change of the color discrimination parameters from baseline to month 6	D15 Fransworth 100 Hue Test	6 months