Levocarnitine for Dry Eye in Sjogren's Syndrome

Vanderbilt University Medical Center

Status and phase

Completed

Phase 2

Conditions

Sjogren's Syndrome

Keratoconjunctivitis Sicca

Treatments

Drug: Levocarnitine

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT03953703

irb200020

Details and patient eligibility

About

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 with all participants receiving both levocarnitine and placebo.

Full description

A phenome wide association study (PheWAS) was conducted for variants in the SLC22A5 gene encoding the OCTN2 protein. OCTN2 is a cell membrane protein that transports carnitine into the cell. The carnitine supplement levocarnitine, FDA approved for human use and with a favorable safety profile, was identified for repurposing. SLC22A5/OCTN2 are a class of sodium ion dependent, high affinity transmembrane proteins expressed in the heart, liver, muscle, and kidney among other tissues. The screen identified "sicca syndrome" (OR 4.56; P = 5.6E-04) as well as various other eye diseases as the most significantly associated phenotypes. Sicca syndrome is defined as dryness of the exocrine glands, particularly the eyes (keratoconjunctivitis sicca) and mouth (xerostomia). This condition is most often caused by Sjogren's syndrome (SjS), a systemic autoimmune disease characterized by lymphocytic infiltration of the lacrimal and salivary glands.

Interestingly, carnitine is present in considerable quantities in the tears of normal, healthy eyes, and studies have shown a decrease in the tear carnitine levels of dry eye patients. Furthermore, eyedrop preparations containing l-carnitine have shown benefit in dry eye disease. The overall hypothesis is that OCTN2 dysfunction underlies keratoconjunctivitis sicca in SjS patients and that oral supplementation with levocarnitine may be beneficial.

Enrollment

15 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Clinician diagnosis of primary or secondary SjS.
Positive anti-SSA
Diagnosis of keratoconjunctivitis sicca defined by OSDI ≥ 25 and Schirmer's test ≤ 5mm/5min in at least 1 eye.
Stable medications for past 4 weeks

Exclusion criteria

Age <18 or >75 at screening visit
Pregnant or nursing, or women of childbearing potential unwilling to use a medically acceptable form of birth control
Unwilling or unable to stop the use of any artificial tear formulations containing L-carnitine.
Taking any form of levocarnitine supplementation or nutritional supplements containing L-carnitine within 2 months prior to enrollment
Unwilling to discontinue immunomodulatory (e.g. Restasis, Xiidra), anti-inflammatory (e.g. steroid containing) eye drops, or serum tears for 1 month prior and throughout the duration of the study
Unwilling to discontinue wearing contact lenses for 1 month prior and throughout the duration of the study
Planned occlusion of the lacrimal puncta with either punctal plugs or cauterization during the study
Laser-assisted in situ keratomileusis (LASIK), photorefractive keratectomy (PRK), or radial keratectomy
Ocular surgery/trauma in the last 6 months or planned during the study
History of ocular infection, including severe blepharitis, in the last 3 months
Active ocular allergy that, in the opinion of the investigator, would compromise interpretation of the data
Elevated AST, ALT, alkaline phosphatase or bilirubin above the upper limit of normal at screening
Renal insufficiency defined by a creatinine clearance of less than 30 ml/min (CKD-EPI or MDRD formula)
Treatment with any investigational agent within ≤ 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of the screening visit
Laboratory parameters at the pre-treatment visit showing any of the following abnormal results: neutrophil count < 1,500/mm3; platelet count < 100,000/mm3; hemoglobin < 9 g/dL
Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product
The patient has a known defect in oxidative phosphorylation (such as a confirmed mitochondrial myopathy)
Any medical or psychiatric condition, which in the opinion of the investigator, places the subject at unacceptable risk or which might compromise the validity of the collected data
Allogeneic BMT or chemotherapy in the past 3 months
The patient has a history of seizure activity.
History of a cornea transplant
Herpes simplex or herpes zoster infection in the eye
Eyelid tattooing (permanent eyelining)
Current diagnoses of any of the following conditions: acute allergic conjunctivitis, inflammation (e.g, retinitis macular inflammation, choroiditis, uveitis, scleritis, episcleritis, keratitis)
On glaucoma eye-drops or eye-drops for lowering eye pressure
Known diagnoses of: Hepatitis C infection, HIV infection, Sarcoidosis, Amyloidosis, Graft versus host disease, Cicatrizing conjunctivitis (e.g. from trachoma, Stevens-Johnson syndrome, pemphigoid, drug induced pseudo-pemphigoid, or chemical ocular burns), Pre-existing lymphoma in patients with no prior diagnosis of SS, Past head and neck radiation treatment
Condition that may compromise ocular surface integrity: trachoma, Stevens-Johnson syndrome, pemphigoid, graft versus host disease, prior chemical burn, recurrent corneal erosions, persistent corneal epithelial defects, prior ocular trauma
Issues with closing eyelids completely or having eyelashes rub on surface of eye
Unwilling to discontinue oral supplements for dry eye like fish oil for 1 month prior and throughout study duration
Unwilling to discontinue use of Tyrvaya (varenicline) nasal spray for 1 month prior and throughout study duration