Lactiplantibacillus Plantarum 299v Probiotic Supplementation in Patients With Diabetic Macular Edema

Lactiplantibacillus Plantarum 299v Probiotic Probiotic Supplementation in Patients With Diabetic Macular Edema

This pilot prospective, interventional, longitudinal study, aims to evaluate the potential benefits of the probiotic supplement Lactobacillus plantarum 299v in patients with diabetic macular edema (DME).

The study seeks to address the following questions:

1. Does central macular thickness on optical coherence tomography decrease after 4 months of supplementation?
2. Is visual acuity improved at 1, 2, 3, and 4 months following initiation of supplementation?
3. Is the number of anti-VEGF injections reduced following initiation of supplementation?

Outcomes will be compared to a control group, using historic retrospective data.

Participants will take Lactobacillus plantarum 299v orally twice daily for four months.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Drug: Lactobacillus plantarum 299v

Detailed Description

Study Design: Prospective open label longitudinal interventional study with oral probiotic supplement Lactobacillus plantarum.

Inclusion criteria: Age of at least 18 years, presence of DME at the current clinical visit

Exclusion criteria: Patients with contraindication to probiotic supplement (e.g. prior allergy or GI intolerance and any type of immunocompromised diseases).

Eligible individuals (patients at least 18 years old with diabetic macular

Participants: Patients with DME that belong in the following two groups:

• Group A: 12 Patients with mild DME and good visual acuity (<= 20/30) similar to DRCR network protocol V that do not need anti-VEGF injections as per standard clinical care.
• Group B: 12 Patients with DME that need anti-VEGF injections as per standard clinical care.

Intervention: Oral probiotic supplement L. plantarum 299v twice daily for 4 months for both groups.

Study outcomes:

• OCT with central macular thickness (CMT) at 1, 2, 3, 4-months follow-up.
• Visual Acuity at 1, 2, 3, 4-months follow-up.
• Number of anti VEGF injections.

In group A, the percentage of patients with a stability or improvement in DME as determined by a stability (+/- 9% of OCT CMT) or a reduction of DME (>= 30 microns or >= 10% decrease of CMT) from baseline will be measured. Secondary endpoints will be visual acuity and need for injection initiation during the 4 months.

In group B, the same outcomes as in group A will be measured. Furthermore, the number of injections group A over the course of 4 months will be evaluated.

Data from both groups will be compared to historical data available at the study site.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Demetrios G. Vavvas, MD PhD; Phone Number: 6175736874; Email: Demetrios_Vavvas@meei.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Mass Eye and Ear
      • Contact: Demetrios G. Vavvas, MD PhD; Phone Number: 617-573-6874; Email: Demetrios_Vavvas@meei.harvard.edu
      • Principal Investigator: Demetrios G. Vavvas, MD PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age of at least 18 years, presence of DME at the current clinical visit

Exclusion Criteria:

• Patients with contraindication to probiotic supplement (e.g. prior allergy or GI intolerance and any type of immunocompromised diseases).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Main Arm - twice daily for 4 months; This is the only arm in this study. All participants will receive 4 months of Lactobacillus plantarum supplementation.	Drug: Lactobacillus plantarum 299v; Lactiplantibacillus Plantarum 299v Probiotic Supplementation, Twice Daily, for 4 Months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Central Macular Thickness	Central macular thickness (CMT) on optical coherence tomography	1,2,3,4-months following supplement initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best corrected visual acuity	Best corrected visual acuity	1, 2, 3, 4-months following supplement initiation
Anti-VEGF Frequency	Number of anti VEGF injections	At 1,2,3,4-months following supplement initiation

Collaborators and Investigators

• Sponsor: Massachusetts Eye and Ear Infirmary

Publications and helpful links

General Publications

• Senger DR, Li D, Jaminet SC, Cao S. Activation of the Nrf2 Cell Defense Pathway by Ancient Foods: Disease Prevention by Important Molecules and Microbes Lost from the Modern Western Diet. PLoS One. 2016 Feb 17;11(2):e0148042. doi: 10.1371/journal.pone.0148042. eCollection 2016.
• Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol. 2007;47:89-116. doi: 10.1146/annurev.pharmtox.46.120604.141046.
• Li JQ, Welchowski T, Schmid M, Letow J, Wolpers C, Pascual-Camps I, Holz FG, Finger RP. Prevalence, incidence and future projection of diabetic eye disease in Europe: a systematic review and meta-analysis. Eur J Epidemiol. 2020 Jan;35(1):11-23. doi: 10.1007/s10654-019-00560-z. Epub 2019 Sep 12.

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: January 26, 2026
• First Submitted That Met QC Criteria: January 26, 2026
• First Posted (Actual): February 3, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: probiotic; diabetic macular edema; Lactiplantibacillus plantarum 299v
• Other Study ID Numbers: 2025P001157

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared. Although data would be de-identified, the small sample size and single-center design increase the risk of re-identification. Therefore, results will be reported in aggregate only. There are no current plans for external sharing of IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No