Ursodeoxycholic Acid for Rhegmatogenous Retinal Detachment (UDCA-RD)

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

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.

Study Overview

• Status: Completed
• Conditions: Rhegmatogenous Retinal Detachment
• Intervention / Treatment: Drug: Ursodeoxycholic Acid

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Lausanne, Switzerland
    • University of Lausanne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 3-5 hours; Duration between oral UDCA intake and surgery of 3-5 hours.	Drug: Ursodeoxycholic Acid
Active Comparator: 6-8 hours; Duration between oral UDCA intake and surgery of 6-8 hours.	Drug: Ursodeoxycholic Acid
Active Comparator: 9-12 hours; Duration between oral UDCA intake and surgery of 9-12 hours.	Drug: Ursodeoxycholic Acid
Active Comparator: > 12 hours; Duration between oral UDCA intake and surgery of >12 hours.	Drug: Ursodeoxycholic Acid
No Intervention: Control; No medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UDCA levels in samples from the vitreous	concentration in ng/ml	0-8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
UDCA levels in samples from the sub retinal fluid	concentration in ng/ml	0-8 months
UDCA levels in samples from the aqueous humor	concentration in ng/ml	0-8 months

Collaborators and Investigators

• Sponsor: Francine Behar-Cohen
• Collaborators: Emory University; University of Lausanne Hospitals

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: July 17, 2016
• First Submitted That Met QC Criteria: July 19, 2016
• First Posted (Estimate): July 22, 2016

Study Record Updates

• Last Update Posted (Actual): April 25, 2019
• Last Update Submitted That Met QC Criteria: April 23, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Eye Diseases; Retinal Diseases; Retinal Detachment; Dissociative Disorders; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodeoxycholic Acid
• Other Study ID Numbers: 2016-00644