Rhegmatogenous Retinal DetachmentPhase 1UDCA-RDNCT02841306
Ursodeoxycholic Acid for Rhegmatogenous Retinal Detachment
A Phase 1 study testing Ursodeoxycholic Acid in people with Rhegmatogenous Retinal Detachment, run by Francine Behar-Cohen at 1 site in Switzerland.
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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Rhegmatogenous Retinal Detachment
- What is being tested?
- Ursodeoxycholic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jul 2016to Sep 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients presenting a rhegmatogenous retinal detachment with more than 4 days from symptoms onset.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Rhegmatogenous Retinal Detachment
- Being tested
- Ursodeoxycholic Acid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ursodeoxycholic AcidDrug
| Study group | Role | What they receive |
|---|---|---|
| 3-5 hours | Active comparator | Duration between oral UDCA intake and surgery of 3-5 hours. Receives: Drug: Ursodeoxycholic Acid |
| 6-8 hours | Active comparator | Duration between oral UDCA intake and surgery of 6-8 hours. Receives: Drug: Ursodeoxycholic Acid |
| 9-12 hours | Active comparator | Duration between oral UDCA intake and surgery of 9-12 hours. Receives: Drug: Ursodeoxycholic Acid |
| > 12 hours | Active comparator | Duration between oral UDCA intake and surgery of >12 hours. Receives: Drug: Ursodeoxycholic Acid |
| Control | No intervention | No medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
UDCA levels in samples from the vitreous
concentration in ng/ml
Measured: 0-8 months
Secondary outcomes (2)
UDCA levels in samples from the sub retinal fluid
concentration in ng/ml
Measured: 0-8 months
UDCA levels in samples from the aqueous humor
concentration in ng/ml
Measured: 0-8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2016 (estimated)
- Study startJul 2016
- Primary completionSep 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rhegmatogenous Retinal DetachmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Francine Behar-Cohen
- Sponsor type
- University, hospital or other
- Collaborators
- University of Lausanne Hospitals, Emory University
- Responsible party
- Sponsor-investigator, Francine Behar-Cohen, University of Lausanne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02841306
- Sponsor's protocol ID
- 2016-00644
- Other IDs
- 2016
- Acronym
- UDCA-RD
- Status last verified
- Apr 2019
- First submitted
- 17 Jul 2016
- Last updated
- 25 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ursodeoxycholic Acid (UDCA) as Adjuvant Treatment for Rhegmatogenous Retinal Detachment: a Phase I Pilot Study
- ClinicalTrials.gov ID
- NCT02841306
- Acronym / sponsor ID
- UDCA-RD / 2016-00644
- Conditions
- Rhegmatogenous Retinal Detachment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Francine Behar-CohenUniversity, hospital or other
- Collaborators
- University of Lausanne Hospitals, Emory University
- Study start
- Jul 2016 (actual)
- Primary completion
- Sep 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 22 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 3-5 hours | Active comparator | Drug: Ursodeoxycholic AcidDuration between oral UDCA intake and surgery of 3-5 hours. |
| 6-8 hours | Active comparator | Drug: Ursodeoxycholic AcidDuration between oral UDCA intake and surgery of 6-8 hours. |
| 9-12 hours | Active comparator | Drug: Ursodeoxycholic AcidDuration between oral UDCA intake and surgery of 9-12 hours. |
| > 12 hours | Active comparator | Drug: Ursodeoxycholic AcidDuration between oral UDCA intake and surgery of >12 hours. |
| Control | No intervention | –No medication |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients presenting a rhegmatogenous retinal detachment with more than 4 days from symptoms onset.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ursodeoxycholic Acid | Drug | 3-5 hours, 6-8 hours, 9-12 hours, > 12 hours |
Primary outcome
UDCA levels in samples from the vitreous
Time frame: 0-8 months
concentration in ng/ml
2 secondary outcomes
UDCA levels in samples from the sub retinal fluid
Time frame: 0-8 months
UDCA levels in samples from the aqueous humor
Time frame: 0-8 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ursodeoxycholic Acid in people with Rhegmatogenous Retinal Detachment, run by Francine Behar-Cohen at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
UDCA levels in samples from the vitreous (time frame: 0-8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2019.