Sjogren's SyndromePhase 2NCT03953703
Levocarnitine for Dry Eye in Sjogren's Syndrome
A Phase 2 study testing Levocarnitine in people with Sjogren's Syndrome and Keratoconjunctivitis Sicca, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Sjogren's Syndrome, Keratoconjunctivitis Sicca
- What is being tested?
- Levocarnitine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Nov 2021to 19 Sep 2025
- Phase
- Phase 2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 30Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: A Randomized Placebo-controlled, Double Blind Pilot Crossover Trial of Levocarnitine for the Treatment of Keratoconjunctivitis Sicca 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 with all participants receiving both levocarnitine and placebo.
Read the detailed 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.
- Conditions
- Sjogren's Syndrome, Keratoconjunctivitis Sicca
- Being tested
- Levocarnitine, Placebo
- Keywords
- Sjogren's syndrome, dry eye, sicca
- Medical subject headings
- Sjogren's Syndrome, Keratoconjunctivitis Sicca, Dry Eye Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevocarnitineDrug
Levocarnitine 1000 mg twice per day for 6 weeks
PlaceboDrug
Placebo 1000 mg twice per day for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Levocarnitine, Placebo | Experimental | 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 Receives: Drug: Levocarnitine; Drug: Placebo |
| Experimental: Placebo, Levocarnitine | Experimental | 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 Receives: Drug: Levocarnitine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change in tear inflammatory cytokine milieu
Levels of inflammatory cytokines IFN-gamma, TNF-alpha, IL-17, IL-6 and IL-1beta will be measured by flow cytometric multiplexed bead assay.
Measured: 14 weeks
Secondary outcomes (10)
Ocular Surface Disease Index (OSDI)
The Ocular Surface Disease Index (OSDI) was developed by the Outcomes Research Group (Allergan Inc.) in 1997 as an assessment of symptoms (functional, limitations, and environmental) of dry eye disease and their effect on vision. It is a 12-item list, with each item compromised of a five category Likert-like response option (see Appendix D). of 24 different clinical and laboratory variables/disease descriptors, comprising nine organ systems. Scores of the descriptors range from 1 to 8, and the total possible score for all descriptors is 105. Regression models are applied to assign relative weights to each parameter.
Measured: 14 weeks
Mean change in tear carnitine levels.
Tear carnitine levels will be measured by mass spectrometry,
Measured: 14 weeks
EULAR Sjogren's Disease Activity Index
The EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SjS developed in 2009. It is a score than has been developed by consensus of experts from European and North American countries and it supported by the EULAR. The ESSDAI includes 12 domains (cutaneous, renal, articular, muscular, peripheral nervous system, hematological, glandular, constitutional, lymphadenopathic, biological) each of which is divided into 3-4 levels of activity.
Measured: 14 weeks
EULAR Sjogren's Syndrome Patient Reported Index
The EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) is a patient-administered questionnaire to asses patients' symptoms. It was developed using the Patient Global Assessment of Disease as the 'gold standard" and measures symptoms of dryness, limb pain, and mental fatigue
Measured: 14 weeks
EULAR Sicca Score
The EULAR sicca score is a measure of overall severity of dryness experienced by the patients. Ocular, oral, cutaneous, nasal, tracheal, and vaginal dryness is reported on a scale of 1-10. The final ESS score is calculated as follows: (2 x oral dryness + ocular dryness) / 3.
Measured: 14 weeks
Patient Global Assessment
The Patient Global Assessment (PGA) is one of the most widely used patient reported outcomes in research. It is typically administered as a single question with either a 1-10 or 1-100 response
Measured: 14 weeks
Schirmer's tear test
The Schirmer's tear test is used to determine if the tear glands produce enough tears to keep the eyes moist. Strips of filter paper are placed within the lower eyelid for a period of time. Wetting of the filter paper is measured in millimeters.
Measured: 14 weeks
Fluorescein staining
Staining with fluorescein is used to characterize dry eye disease, assess severity, and monitor response to therapy. It is graded using the Oxford scale which consists of a chart containing a series of panels labeled A-E in order of increasing severity. Staining is represented by punctate dots, and the number of dots increases by one log unit from panel A to B and by 0.5 log units between panels B to E. To grade, comparisons are made between the panels and the appearance of staining on the conjunctiva and cornea of the patient.
Measured: 14 weeks
Lissamine green staining
Staining with lissamine green is used to characterize dry eye disease, assess severity, and monitor response to therapy. It is graded using the Oxford scale which consists of a chart containing a series of panels labeled A-E in order of increasing severity. Staining is represented by punctate dots, and the number of dots increases by one log unit from panel A to B and by 0.5 log units between panels B to E. To grade, comparisons are made between the panels and the appearance of staining on the conjunctiva and cornea of the patient.
Measured: 14 weeks
Tear break-up time
Tear break-up time is measured by adding fluorescein dye to the eye and observing the tear film using a slit lamp until dry spots occur.
Measured: 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2019
- Study start17 Nov 2021
- Primary completion19 Sep 2025
- Study completion19 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sjogren's SyndromeStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christine Shieh, Vanderbilt University Medical Center
- Investigators
- Christine Shieh, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03953703
- Sponsor's protocol ID
- irb200020
- Status last verified
- Nov 2025
- First submitted
- 30 Apr 2019
- Last updated
- 4 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Placebo-controlled, Double Blind Pilot Crossover Trial of Levocarnitine for the Treatment of Keratoconjunctivitis Sicca in Sjogren's Syndrome
- ClinicalTrials.gov ID
- NCT03953703
- Acronym / sponsor ID
- irb200020
- Conditions
- Sjogren's Syndrome, Keratoconjunctivitis Sicca
- Keywords
- Sjogren's syndrome, dry eye, sicca
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- 17 Nov 2021 (actual)
- Primary completion
- 19 Sep 2025 (actual)
- Study completion
- 19 Sep 2025 (actual)
- First posted
- 16 May 2019 (actual)
- 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.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental: Levocarnitine, Placebo | Experimental | Drug: Levocarnitine, Drug: Placebo1000 mg of levocarnitine twice per day for six weeks, a two week washout period, 1000 mg of placebo twice per day for 6 weeks |
| Experimental: Placebo, Levocarnitine | Experimental | Drug: Levocarnitine, Drug: Placebo1000 mg of placebo twice per day for six weeks, a two week washout period, 1000 mg of levocarnitine twice per day for 6 weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (30 listed)
- 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
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 |
|---|---|---|
| LevocarnitineLevocarnitine 1000 mg twice per day for 6 weeks | Drug | Experimental: Levocarnitine, Placebo, Experimental: Placebo, Levocarnitine |
| PlaceboPlacebo 1000 mg twice per day for 6 weeks | Drug | Experimental: Levocarnitine, Placebo, Experimental: Placebo, Levocarnitine |
Primary outcome
Mean change in tear inflammatory cytokine milieu
Time frame: 14 weeks
Levels of inflammatory cytokines IFN-gamma, TNF-alpha, IL-17, IL-6 and IL-1beta will be measured by flow cytometric multiplexed bead assay.
10 secondary outcomes
Ocular Surface Disease Index (OSDI)
Time frame: 14 weeks
Mean change in tear carnitine levels.
Time frame: 14 weeks
EULAR Sjogren's Disease Activity Index
Time frame: 14 weeks
EULAR Sjogren's Syndrome Patient Reported Index
Time frame: 14 weeks
EULAR Sicca Score
Time frame: 14 weeks
Patient Global Assessment
Time frame: 14 weeks
Schirmer's tear test
Time frame: 14 weeks
Fluorescein staining
Time frame: 14 weeks
Lissamine green staining
Time frame: 14 weeks
Tear break-up time
Time frame: 14 weeks
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 4 Dec 2025.
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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.
Christine Shieh, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Levocarnitine in people with Sjogren's Syndrome and Keratoconjunctivitis Sicca, run by Vanderbilt University Medical Center at 1 site in United States.
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 4 inclusion and 30 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 4 Dec 2025. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Mean change in tear inflammatory cytokine milieu (time frame: 14 weeks). 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 4 Dec 2025.