Lamivudine and Plasma Markers of Inflammation in Retinal Detachment

Intra-ocular Penetration of Oral Lamivudine and Measurement of Systemic Inflammatory Markers in Patients Undergoing Rhegmatogenous Retinal Detachment Surgery

The goal of this clinical trial is to test whether an oral medication (lamivudine) enters the eye and reduces blood markers of inflammation in people who undergo retinal detachment surgery (pars plana vitrectomy).

Participants will take the study medication or placebo, and the researchers will measure blood markers of inflammation before and after surgery. The researchers will also measure the amount of medication in the blood and fluid inside the participant's eye (which is collected during surgery).

Study Overview

• Status: Recruiting
• Conditions: Rhegmatogenous Retinal Detachment; Retinal Detachment
• Intervention / Treatment: Drug: Lamivudine 300 MG; Drug: Placebo

Detailed Description

Lamivudine is an anti-viral medication that has intrinsic anti-inflammatory properties that could be useful in the treatment of vitreoretinal disease. It is not known whether lamivudine enters the eye after oral administration. The purpose of this study is to measure the intra-ocular concentration of lamivudine after oral administration in participants that require pars plana vitrectomy surgery for repair of rhegmatogenous retinal detachment. Participants undergoing retinal detachment surgery will receive oral lamivudine for three days prior to surgery; lamivudine will be measured intra-operatively (vitreous and aqueous humor) and pre-operatively (plasma). Plasma markers of inflammation will be measured before and after surgery.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Angie Adler; Phone Number: 608-265-7557; Email: amadler1@wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Recruiting
      • University of Wisconsin
      • Principal Investigator: Michael Altaweel, MD
      • Contact: Angie Adler; Phone Number: 608-265-7557; Email: amadler1@wisc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 or ≤ 65 years
• Patients with rhegmatogenous retinal detachment that require vitrectomy surgery

Exclusion Criteria:

• Previous pars plana vitrectomy in the affected eye
• Positive for Hepatitis B surface antigen or HIV antibodies, or history of Hepatitis B/HIV
• Pregnant or breast-feeding
• Liver disease or abnormal AST/ALT
• Renal impairment (Creatinine clearance < 50)
• Diabetes with current use of insulin
• Anemia (Hemoglobin <13.2 g/dL (male) or < 11.6 g/dL (female))
• Unwilling to hold concurrent use of sorbitol or sorbitol-containing medications or products while taking study medication(including, but not limited to: blackberries, raspberries, strawberries, stone fruits, apples, avocados, sugar-free items such as chewing gum, hard candies, snack bars, frozen desserts, and chocolates, liquid and capsule/caplet analgesics, cough/cold/flu syrup, liquid and capsule/caplet pseudoephedrine, chewable antacid tablets, liquid and capsule allergy medications, motion sickness and nausea medications)
• Current use of trimethoprim-sulfamethoxazole
• Pancreatitis or history of pancreatitis
• Uncontrolled blood pressure (> 160 mm Hg systolic or >100 mm Hg diastolic) within the last 3 months, or current use of more than one anti-hypertensive medication
• History of stroke, myocardial infarction, or congestive heart failure
• Current vitreous hemorrhage that obscures view of retinal details
• Patients with a shallow anterior chamber or in whom anterior chamber paracentesis is considered unsafe

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lamivudine; Lamivudine 300mg PO once daily for three days	Drug: Lamivudine 300 MG; Drug to be taken once daily for three days (two days prior to surgery and on the morning of surgery)
Placebo Comparator: Placebo; Placebo once daily for three days	Drug: Placebo; Dose to be taken once daily for three days (two days prior to surgery and on the morning of surgery)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of lamivudine after oral administration	Mean concentration of lamivudine in plasma	Pre-operative
Intra-ocular concentration of lamivudine after oral administration	Mean concentration of lamivudine in vitreous and aqueous humor	Intra-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in erythrocyte sedimentation rate (millimeter per hour)	Mean concentration of inflammatory markers will in part be measured by erythrocyte sedimentation rate.	Pre-operative to one week post-operative
Change in C-reactive protein (milligrams per liter)	Mean concentration of inflammatory markers will in part be measured by C-reactive protein.	Pre-operative to one week post-operative
Change in concentration of inflammatory markers (picogram per milliliter)	Mean concentration of inflammatory markers will in part be measured by tumor necrosis factor alpha, interleukin (IL)-18, IL-1 beta, IL-6, IL-10, MCP-1, MIP-1 alpha, GM-CSF in picograms per milliliter.	Pre-operative to one week post-operative
Change in concentration of inflammatory markers (micrograms per milliliter)	Mean concentration of inflammatory markers will in part be measured by interferon (IFN) alpha, IFN beta, IFN gamma in micrograms per milliliter)	Pre-operative to one week post-operative
Change in concentration of soluble IL-2 receptor alpha (Units per milliliter)	Mean concentration of inflammatory markers will in part be measured by soluble IL-2 receptor alpha in Units per milliliter.	Pre-operative to one week post-operative

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Michael Altaweel, MD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2024
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: August 1, 2023
• First Submitted That Met QC Criteria: September 20, 2023
• First Posted (Actual): September 28, 2023

Study Record Updates

• Last Update Posted (Actual): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: vitrectomy surgery
• Additional Relevant MeSH Terms: Mental Disorders; Eye Diseases; Retinal Diseases; Retinal Detachment; Dissociative Disorders; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Lamivudine
• Other Study ID Numbers: 2022-1223; SMPH/OPHTHAL&VIS SCI/FPRC (Other Identifier: UW Madison); Protocol Version 1/29/2024 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes