Levocarnitine for Dry Eye in Sjogren's Syndrome

Overseen By Alyssa R Merkel, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Must not be taking: Levocarnitine, Immunomodulatory eye drops

Disqualifiers: Pregnancy, Renal insufficiency, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 14 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests levocarnitine to determine its effectiveness in alleviating dry eye symptoms in individuals with Sjogren's syndrome, a condition affecting moisture-producing glands. Participants will take both levocarnitine and a placebo (a pill with no active drug) at different times to compare effects. Eligible participants must have a confirmed diagnosis of Sjogren's syndrome and significant dry eye issues. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop certain medications. You must discontinue immunomodulatory, anti-inflammatory eye drops, serum tears, oral supplements for dry eye like fish oil, and Tyrvaya nasal spray for 1 month before and during the study. You also cannot use artificial tears with L-carnitine or take levocarnitine supplements 2 months prior to enrollment.

Will I have to stop taking my current medications?

Yes, you will need to stop using certain medications like immunomodulatory and anti-inflammatory eye drops, serum tears, and oral supplements for dry eye at least 1 month before and during the study. You also cannot use artificial tears containing L-carnitine or take any levocarnitine supplements.

Is there any evidence suggesting that levocarnitine is likely to be safe for humans?

Research has shown that the FDA has approved levocarnitine for use in people, indicating it is generally considered safe. This approval means it has undergone testing for other conditions and passed safety checks. However, specific safety information for treating dry eye in Sjogren's syndrome is not available.

Levocarnitine, a supplement, usually has a good safety record, allowing most people to take it without major issues. Participants in the trial who experience side effects are likely to find them mild. Common side effects from similar supplements might include an upset stomach, but these are typically not serious.

Overall, current information suggests levocarnitine is safe to use, but as with all supplements, monitoring your body's reactions is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for dry eye in Sjogren's syndrome?

Unlike the standard treatments for dry eye in Sjogren's Syndrome, which often include artificial tears and anti-inflammatory medications, levocarnitine offers a fresh approach by utilizing a compound that plays a key role in cellular energy production. Researchers are excited because levocarnitine might improve eye lubrication through a different mechanism, potentially offering relief for patients who don’t respond well to existing options. The dual-phase treatment, alternating between levocarnitine and placebo, is designed to highlight its effectiveness, which could lead to a novel therapeutic option for managing this uncomfortable condition.

What evidence suggests that levocarnitine might be an effective treatment for dry eye in Sjogren's syndrome?

Research has shown that levocarnitine might help alleviate dry eye symptoms. In animal studies, levocarnitine increased tear production and improved eye health in mice with dry eye disease. This trial will evaluate levocarnitine's potential benefits for eye health in humans with Sjogren's syndrome. Participants will receive either levocarnitine or a placebo in different sequences to assess its effectiveness. Although more research with humans is needed, these early results offer promise for those with Sjogren's syndrome. ^{1 2 5 6 7}

Who Is on the Research Team?

Christine Shieh, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

Adults with Sjogren's syndrome and dry eye, confirmed by specific tests (OSDI ≥ 25, Schirmer's ≤ 5mm/5min), can join this trial. They must have stable medications for the past month but cannot be using certain eye drops or contact lenses, have had recent ocular surgery, or suffer from severe liver or kidney issues.

Inclusion Criteria

I have been diagnosed with Sjögren's syndrome.

I have been diagnosed with dry eye syndrome, confirmed by specific eye tests.

I have been diagnosed with dry eye syndrome.

Exclusion Criteria

You have had a serious eye infection, like severe blepharitis, in the past 3 months.

I have had a cornea transplant.

Active ocular allergy that, in the opinion of the investigator, would compromise interpretation of the data

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 1000 mg of levocarnitine or placebo twice per day for six weeks, followed by a two-week washout period, then crossover to the alternate treatment for another six weeks

14 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Levocarnitine
• Placebo

Trial Overview The study is testing Levocarnitine against a placebo to see if it helps with dry eyes in Sjogren's patients. Everyone will get both treatments at different times because it’s a crossover study – meaning participants switch between the drug and placebo.

How Is the Trial Designed?

Group I: Experimental: Placebo, Levocarnitine Experimental Treatment 2 Interventions

1000 mg of placebo twice per day for six weeks, a two week washout period, 1000 mg of levocarnitine twice per day for 6 weeks

Group II: Experimental: Levocarnitine, Placebo Experimental Treatment 2 Interventions

1000 mg of levocarnitine twice per day for six weeks, a two week washout period, 1000 mg of placebo twice per day for 6 weeks

Levocarnitine is already approved in United States, European Union for the following indications:

Approved in United States as Carnitor for:

• Carnitine deficiency
• Hyperlipoproteinemia

Approved in European Union as Levocarnitine for:

• Carnitine deficiency
• Hyperlipoproteinemia

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

Tear samples from 10 healthy subjects and 10 patients with dry eye syndrome (DES) revealed that carnitine levels were significantly lower in DES patients, suggesting a potential deficiency that could contribute to the condition.

The study proposes that carnitine may play a protective role in maintaining tear film osmolarity, and suggests that carnitine solutions could be explored as a treatment option for alleviating the effects of hyperosmolarity in DES.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-carnitine and short chain ester in tears from patients with dry eye. Pescosolido, N., Imperatrice, B., Koverech, A., et al.[2022]

Fenofibrate significantly reduced inflammation in the lacrimal glands and improved tear secretion in a mouse model of Sjögren syndrome, indicating its potential efficacy in treating autoimmune dry eye.

The mechanism of action involves the modulation of immune responses, specifically decreasing Th1 and Th17 cells while increasing Treg cells, through the activation of PPAR-α and LXR-β signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PPAR-α Agonist Fenofibrate Ameliorates Sjögren Syndrome-Like Dacryoadenitis by Modulating Th1/Th17 and Treg Cell Responses in NOD Mice. Guo, X., Dang, W., Li, N., et al.[2022]

In a study of 249 patients with Sjögren syndrome, significant ocular surface changes were observed, including meibomian gland dysfunction in 46% and severe dry eye symptoms, which negatively impacted visual acuity.

Patients with secondary Sjögren syndrome due to rheumatoid arthritis experienced the worst outcomes in terms of dry eye severity and visual complications, highlighting the need for targeted management in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of ocular surface damage and visual impact in patients with primary and secondary Sjögren syndrome. Villarreal-Gonzalez, AJ., Jocelyn Rivera-Alvarado, I., Rodriguez-Gutierrez, LA., et al.[2021]

In a study of 60 patients with primary Sjögren's syndrome, the addition of Carbopol 974P significantly improved symptoms of keratoconjunctivitis sicca (KCS) after 12 weeks, with a notable reduction in dry eye symptoms and ocular lesions.

Carbopol 974P was well-tolerated with no reported adverse events, indicating it is a safe and effective option for patients who do not respond adequately to standard artificial tears.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of Carbopol 974P (Siccafluid) in the treatment of severe to moderate keratoconjunctivitis sicca in patients with primary Sjögren's syndrome not responding to standard treatment with artificial tears]. Ostuni, P., Battista, ME., Furlan, A.[2019]

Topical application of the integrin α4 antagonist GW559090 significantly improved corneal barrier integrity and reduced inflammation in a mouse model of dry eye associated with Sjögren's syndrome, showing greater efficacy than the vehicle control.

Both GW559090 and dexamethasone treatments led to reduced corneal fluorescein staining and increased conjunctival goblet cell density, indicating effective management of ocular surface inflammation and improved eye health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sjögren's syndrome associated dry eye in a mouse model is ameliorated by topical application of integrin α4 antagonist GW559090. Contreras-Ruiz, L., Mir, FA., Turpie, B., et al.[2016]

Androgens play a crucial role in regulating the function of the meibomian gland, which is important for maintaining a stable tear film, as evidenced by the presence of androgen receptors and their impact on lipid production in animal models.

Androgen deficiency is linked to meibomian gland dysfunction and evaporative dry eye, particularly in women with Sjögren's syndrome, suggesting that addressing androgen levels could be important for managing dry eye symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen deficiency, Meibomian gland dysfunction, and evaporative dry eye. Sullivan, DA., Sullivan, BD., Evans, JE., et al.[2022]

In a study involving 60 female mice, L-carnitine eye drops significantly protected the corneal and conjunctival epithelium from damage caused by hyperosmolar saline, as evidenced by improved goblet cell counts and corneal thickness compared to control groups.

After 28 days of treatment, mice receiving L-carnitine showed lower tear osmolarity and better corneal surface integrity, suggesting that L-carnitine could be a beneficial intervention for dry eye conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A primary study of L-carnitine protective effect on corneal and conjunctival epithelium of mouse dry eye model induced by hyperosmolar saline]. Huo, J., Xie, HP., Li, J., et al.[2015]

Androgen deficiency is believed to play a significant role in the development of dry eye symptoms in Sjögren's syndrome, an autoimmune disorder primarily affecting women.

Topical androgen treatment has been shown to enhance the function of both lacrimal and meibomian glands, suggesting it could be a safe and effective therapy for alleviating dry eye symptoms associated with Sjögren's syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgens and dry eye in Sjögren's syndrome. Sullivan, DA., Wickham, LA., Rocha, EM., et al.[2019]

In a study involving 170 subjects with dry eye disease, VVN001 Ophthalmic Solution showed no major safety concerns, with only minor adverse effects reported, such as instillation site pain and dysgeusia.

While the primary efficacy outcomes were not statistically significant, VVN001 5% did show some positive effects on secondary measures like total corneal fluorescein staining and Schirmer score, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2a, double-masked, randomized, vehicle-controlled trial of VVN001 in subjects with dry eye disease. Tauber, J., Evans, D., Segal, B., et al.[2023]

L-carnitine plays a crucial role in fatty acid oxidation and may improve insulin sensitivity in diabetic patients, potentially protecting against diabetic retinopathy due to its antioxidant and antiapoptotic properties.

Acetyl-L-carnitine has shown significant benefits in improving retinal damage and visual acuity in patients with retinal artery occlusion, suggesting its clinical utility in various ocular conditions related to systemic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular disorders secondary to systemic disease and the potential role of carnitines. Pescosolido, N., Imperatrice, B., Karavitis, P.[2018]

Topical low-dose hydrocortisone sodium phosphate (PFH) significantly improved symptoms and signs of dry eye disease in patients with Sjögren syndrome, as evidenced by reductions in conjunctival hyperemia and corneal staining over a 6-month period.

The treatment was found to be safe, with no significant changes in intraocular pressure, indicating that PFH can be an effective option for managing dry eye symptoms without compromising eye health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term results of a pulsed therapy with hydrocortisone eye drops to treat moderate to severe dry eye in primary Sjögren syndrome patients. Menchini, M., Sartini, F., Figus, M., et al.[2023]

In a study of 8 patients with Sjögren syndrome, oral pilocarpine significantly improved tear meniscus height and symptoms of dry eye and dry mouth over a 3-month period, as measured by various assessments including OCT and visual analog scales.

The use of Visante optical coherence tomography (OCT) proved effective for noninvasive monitoring of tear meniscus changes, showing significant improvements as early as 1 week after starting treatment with pilocarpine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Visante optical coherence tomography and tear function test evaluation of cholinergic treatment response in patients with sjögren syndrome. Ibrahim, OM., Dogru, M., Kawashima, S., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03953703

Levocarnitine for Dry Eye in Sjogren's Syndrome This study evaluates the effectiveness of levocarnitine in the treatment of dry eye in adults with Sjogren's syndrome. This will be a crossover study design ...

2. vanderbilt.trialstoday.org vanderbilt.trialstoday.org/trial/NCT03953703

Levocarnitine for Dry Eye in Sjogren's Syndrome This study evaluates the effectiveness of levocarnitine in the treatment of dry eye in adults with Sjogren's syndrome.

3. trialx.com trialx.com/clinical-trials/listings/270196/levocarnitine-for-dry-eye-in-sjogrens-syndrome/

Levocarnitine for Dry Eye in Sjogren's Syndrome Overview. This study evaluates the effectiveness of levocarnitine in the treatment of dry eye in adults with Sjogren's syndrome.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8188229/

Topical Delivery of Levocarnitine to the Cornea and Anterior ... LCTG administration for 3 days can significantly increase the amount of tear secretion in mice with DED, promote corneal epithelial integrity and central ...

5. withpower.com withpower.com/trial/phase-3-keratoconjunctivitis-8-2021-4fd3b

Levocarnitine for Dry Eye in Sjogren's Syndrome This trial tests levocarnitine, a supplement that helps transport carnitine into cells, in adults with Sjogren's syndrome who have dry eyes.

6. imgcdn.mckesson.com imgcdn.mckesson.com/CumulusWeb/Click_and_learn/SDS_9NVTMP_LEVOCARNITINE_SOL_100MG_ML_4OZ_CHERRY.pdf

SDS: Levocarnitine Oral Solution, USP P280 Wear protective gloves/eye protection/ face protection. P370 In case of fire: Use water, carbon dioxide, dry. + chemical or foam as necessary to extinguish ...

7. trials.arthritis.org trials.arthritis.org/trials/NCT03953703

Levocarnitine for Dry Eye in Sjogren's Syndrome This study evaluates the effectiveness of levocarnitine in the treatment of dry eye in adults with Sjogren's syndrome. This will be a crossover study design ...