Ursodeoxycholic Acid for Rhegmatogenous Retinal Detachment

Rhegmatogenous Retinal Detachment Clinical Trial

— UDCA-RD  

Official title:

Ursodeoxycholic Acid (UDCA) as Adjuvant Treatment for Rhegmatogenous Retinal Detachment: a Phase I Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02841306
• Other study ID #: 2016-00644
• Status: Completed
• Phase: Phase 1
• Start date: July 2016
• Est. completion date: September 2017

Study information

• Verified date: April 2019
• Source: University of Lausanne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

26 patients presenting a rhegmatogenous retinal detachment with more than 4 days of duration will be prospectively included.

A single dose of ursodeoxycholic acid will be administered orally before surgery at different time-points in 22 subjects. Standard surgery will be performed and ocular samples will be collected during the procedure. Ursodeoxycholic acid treatment will be continued in treated patients during 3 months after surgery.

Ocular and serum samples from the 4 untreated patients will serve as negative controls for the determination of UDCA levels.

Description:

Retinal detachments consist in a separation of the neuroretina from the retinal pigment epithelium. The most common form is rhegmatogenous retinal detachment (RRD), which occurs as a result of a full-thickness retinal break and the presence of vitreoretinal tractions. Photoreceptor cell death occurs rapidly after RRD and is the ultimate cause of vision loss in these patients. Reattachment of the retina by a surgical procedure allows a recovery of vision. However, the degree of visual recovery differs among patients, despite successful reattachment. This is mainly related to the preoperative visual acuity level, the presence of a macular detachment and its duration. Predicting factors of worse visual acuity are the height of retinal detachment in the macula and the presence of edema, separation, cyst and undulation at the level of the outer nuclear layer showed by optical coherence tomography (OCT). Most patients usually consult with a RRD already involving the macular area after 3 days or more, leading to a worse visual prognostic even with successful surgery. The need for adjuvant neuroprotective agents is then critical to improve photoreceptor survival, functional recovery and subsequent quality of life in patients affected by RRD.

Tauroursodeoxycholic acid (TUDCA) is the taurine conjugate of ursodeoxycholic acid (UDCA), a secondary bile acid produced by intestinal bacteria. UDCA was approved by the Food and Drug Administration (FDA) for the treatment of cholestatic liver disease. Both UDCA and TUDCA are potent inhibitors of apoptosis, in part by interfering with the upstream mitochondrial pathway of cell death, inhibiting oxygen-radical production, reducing endoplasmic reticulum (ER) stress, and stabilizing the unfolded protein response (UPR). TUDCA has been proposed as anti-apoptotic agent in several neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's, Parkinson's, and Huntington's diseases.

In certain degenerative retinal disorders, such as retinitis pigmentosa, TUDCA plays an important role in preventing cell death. In an animal model of RRD, systemic treatment by TUDCA has been shown to protect photoreceptors from cell death.

The aim of this study is to determine whether detectable levels of UDCA reach the vitreous cavity when administered orally at different time points before surgery for RRD, and to analyze its ocular safety.

20 patients presenting a rhegmatogenous retinal detachment with more than 4 days of duration will be prospectively included.

A single dose of ursodeoxycholic acid will be administered orally before surgery at different time-points in 16 subjects. Standard surgery will be performed and ocular samples will be collected during the procedure. Ursodeoxycholic acid treatment will be continued in treated patients during 3 months after surgery.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Patients presenting a rhegmatogenous retinal detachment with more than 4 days from symptoms onset.

Exclusion Criteria:

• Previous vitrectomy, vitreous bleeding, other associated retinal disease.

• Monophthalmic patients.

• Pregnancy and lactation, peptic ulcer, acute or chronic liver disease, acute infection of the gallbladder and biliary tract, repeated biliary colic, Crohn's disease, ulcerative colitis, or other disease of the small intestine and colon, and hypersensitivity.

• Patients treated by Cholestyramine, Colestipol and Antacids containing aluminum hydroxide or magnesium, Cyclosporine, Ciprofloxacin, Nitrendipine, Dapsone.

• Patients presenting with galactose intolerance, the Lapp lactase deficiency or glucose and galactose malabsorption.

Related Conditions & MeSH terms

• Dissociative Disorders
• Retinal Detachment
• Rhegmatogenous Retinal Detachment

Intervention

Drug:
• Ursodeoxycholic Acid

Locations

Country	Name	City	State
Switzerland	University of Lausanne	Lausanne

Sponsors (3)

Lead Sponsor	Collaborator
Francine Behar-Cohen	Emory University, University of Lausanne Hospitals

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	UDCA levels in samples from the vitreous	concentration in ng/ml	0-8 months
Secondary	UDCA levels in samples from the sub retinal fluid	concentration in ng/ml	0-8 months
Secondary	UDCA levels in samples from the aqueous humor	concentration in ng/ml	0-8 months