Multiple SclerosisPhase 2NCT05957913
Effects of Antiviral Therapies on Epstein-Barr Virus Replication
A Phase 2 study testing Truvada (tenofovir/emtricitabine) in people with Multiple Sclerosis, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This research study is being performed to find out if Truvada (tenofovir/emtricitabine), an antiviral drug with activity against the Epstein Barr virus (EBV), can reduce EBV levels in saliva and blood in people with multiple sclerosis (MS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Truvada (tenofovir/emtricitabine)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jun 2023to 31 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent form
- Stated willingness and ability to comply with all study procedures and availability for the duration of the study
- Age: 18+
- Established diagnosis of multiple sclerosis
- Evidence of Epstein Barr virus (EBV) infection by serological testing for EBV antibodies antibodies (subjects will have EBV testing performed at the pre-screening visit and if serologies are negative, the subjects will be removed from the study)
Who cannot join
- Pregnancy or lactation
- Known allergic reactions to components of Truvada
- Previous treatment with Truvada or Descovy
- Unknown HIV status (subjects must have completed HIV antigen/antibody and viral load testing within the prior 6 months to being enrolled or have the testing completed at the pre-screening visit)
- Active or latent hepatitis B (HBV) (subjects must have completed HBV serologies - HbsAg, anti-HBs, and anti-HBc - within the prior 6 months to being enrolled or have the testing completed at the pre-screening visit)
- Current symptoms of severe, progressive, or uncontrolled renal, hematologic, gastrointestinal, pulmonary, cardiac, or neurologic disease, or other medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study
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- Creatinine clearance (CrCl) <75mL/min, as calculated by the Cockcroft-Gault equation
- Urine dipstick for protein and glucose, excluding values of "1 +" or greater
- Any history of bone fractures not explained by trauma
- Confirmed Grade 2 or greater hypophosphatemia
- Any Grade 2 or greater toxicity on screening tests and assessments
- Taking a medication with known interactions with Truvada including but not limited to: Acyclovir, valacyclovir, adefovir, cabozantinib, carbamazepine, cidofovir, cladribine, cobicistat, diclofenac, multiple non-steroidal antiinflammatories (NSAIDs) or chronic high dose NSAIDs, fosphenytoin or phenytoin, ganciclovir, valganciclovir, oxcarbazepine, phenobarbital, primidone, rifabutin, rifampin, rifapentine, sofosbuvir, tipranavir, or other drugs that significantly affect renal function
- Current treatment with drugs known to affect EBV replication as listed below: Acyclovir, valacyclovir, ganciclovir, valganciclovir, famciclovir, teriflunomide, interferon
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
This research study is being performed to find out if Truvada (tenofovir/emtricitabine), an antiviral drug with activity against the Epstein Barr virus (EBV), can reduce EBV levels in saliva and blood in people with multiple sclerosis (MS). A second goal is to find out if Truvada (tenofovir/ emtricitabine) is safe and tolerable in people with MS.
Read the detailed description
The proposed trial is built on the premise that multiple sclerosis (MS) is, in part, triggered by infection with the human herpesvirus Epstein Barr virus (EBV), and that targeting the virus could be a more effective and safer strategy for MS treatment than immunomodulation or immunosuppression alone. The evidence supporting a causal role for EBV in MS initially came from epidemiological studies that showed similarities in the distribution of infectious mononucleosis and MS, a 2-3 fold increased MS risk among individuals with a clinical history of infectious mononucleosis, and by compelling evidence that MS rarely, if ever, develops in individuals who are not infected with EBV. Furthermore, in a longitudinal study based on the Department of Defense Serum Repository with samples from over 7 million young adults free of MS, individuals who were EBV-seronegative at baseline did not develop symptoms of MS until at least several months after EBV seroconversion, and high serum antibody titers against the EBV-encoded nuclear antigen-1 were associated with an over 30-fold increase in MS risk.
Antiviral agents repurposed from treating other herpesviruses, like acyclovir or valacyclovir, have had minimal clinical efficacy against EBV in studies for infectious mononucleosis and multiple sclerosis. Prodrugs of tenofovir, such as tenofovir disoproxil fumarate (TDF), are significantly more potent inhibitors of EBV replication in cell culture than other drugs that have been clinically ineffective for EBV. TDF is a safe drug used clinically for HIV pre-exposure prophylaxis (PrEP) in HIV-negative patients as the drug Truvada. Truvada has been widely used since its approval in 2004 for the treatment of human immunodeficiency virus (HIV), and has a well-known safety profile that makes it a good candidates for clinical studies.
- Conditions
- Multiple Sclerosis
- Being tested
- Truvada (tenofovir/emtricitabine)
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Truvada (tenofovir/emtricitabine)Drug
Also called TDF
Doses and route of administration of the study drug will be kept the same as for the FDA-approved indication of HIV-1 prevention in healthy individuals. The study drug is not FDA-approved for the treatment of multiple sclerosis.
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | After a one-month baseline period where patients will not take any study drug, all patients will receive Truvada (tenofovir/emtricitabine) for three months. The study drug will be Truvada (tenofovir/emtricitabine), an antiviral drug that is approved by the Food \& Drug Administration (FDA) for the treatment of chronic hepatitis B virus and for the treatment and prevention of human immunodeficiency virus (HIV) infection. The study drug will be administered at the standard dose used for the treatment and prevention of HIV (300mg tenofovir disoproxil fumarate, 200mg emtricitabine). Since extensive safety and tolerability data already exists for this standard dose, the selection of this dose also allows us to use existing data to inform strategies for safety and tolerability monitoring to minimize risk, as detailed in the study design. Receives: Drug: Truvada (tenofovir/emtricitabine) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Epstein Barr virus (EBV) viral load
EBV viral load will be quantified in saliva and peripheral blood using a sensitive assay.
Measured: Change from baseline at three months
Secondary outcomes (2)
Tolerability of Truvada (tenofovir/emtricitabine)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Measured: Change from baseline at three months
Fatigue
Fatigue will be measured using a standardized survey scale where higher scores indicate more fatigue
Measured: Change from baseline at three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2023
- Study start5 Jun 2023
- Primary completion4 Jun 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The study design will be an open-label single arm study.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Solving MS
- Responsible party
- Principal investigator, Michael, Levy M.D.,Ph.D., Massachusetts General Hospital
- Investigators
- Michael Levy, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05957913
- Sponsor's protocol ID
- 2023P000828
- Status last verified
- Jul 2026
- First submitted
- 28 Jun 2023
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Antiviral Therapies on Epstein-Barr Virus Replication
- ClinicalTrials.gov ID
- NCT05957913
- Acronym / sponsor ID
- 2023P000828
- Conditions
- Multiple Sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Solving MS
- Study start
- 5 Jun 2023 (actual)
- Primary completion
- 4 Jun 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 24 Jul 2023 (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 research study is being performed to find out if Truvada (tenofovir/emtricitabine), an antiviral drug with activity against the Epstein Barr virus (EBV), can reduce EBV levels in saliva and blood in people with multiple sclerosis (MS). A second goal is to find out if Truvada (tenofovir/ emtricitabine) is safe and tolerable in people with MS.
Detailed description
The proposed trial is built on the premise that multiple sclerosis (MS) is, in part, triggered by infection with the human herpesvirus Epstein Barr virus (EBV), and that targeting the virus could be a more effective and safer strategy for MS treatment than immunomodulation or immunosuppression alone. The evidence supporting a causal role for EBV in MS initially came from epidemiological studies that showed similarities in the distribution of infectious mononucleosis and MS, a 2-3 fold increased MS risk among individuals with a clinical history of infectious mononucleosis, and by compelling evidence that MS rarely, if ever, develops in individuals who are not infected with EBV. Furthermore, in a longitudinal study based on the Department of Defense Serum Repository with samples from over 7 million young adults free of MS, individuals who were EBV-seronegative at baseline did not develop symptoms of MS until at least several months after EBV seroconversion, and high serum antibody titers against the EBV-encoded nuclear antigen-1 were associated with an over 30-fold increase in MS risk.
Antiviral agents repurposed from treating other herpesviruses, like acyclovir or valacyclovir, have had minimal clinical efficacy against EBV in studies for infectious mononucleosis and multiple sclerosis. Prodrugs of tenofovir, such as tenofovir disoproxil fumarate (TDF), are significantly more potent inhibitors of EBV replication in cell culture than other drugs that have been clinically ineffective for EBV. TDF is a safe drug used clinically for HIV pre-exposure prophylaxis (PrEP) in HIV-negative patients as the drug Truvada. Truvada has been widely used since its approval in 2004 for the treatment of human immunodeficiency virus (HIV), and has a well-known safety profile that makes it a good candidates for clinical studies.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study design will be an open-label single arm study.
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: Truvada (tenofovir/emtricitabine)After a one-month baseline period where patients will not take any study drug, all patients will receive Truvada (tenofovir/emtricitabine) for three months. The study drug will be Truvada (tenofovir/emtricitabine), an antiviral drug that is approved by the Food \& Drug Administration (FDA) for the treatment of chronic hepatitis B virus and for the treatment and prevention of human immunodeficiency virus (HIV) infection. The study drug will be administered at the standard dose used for the treatment and prevention of HIV (300mg tenofovir disoproxil fumarate, 200mg emtricitabine). Since extensive safety and tolerability data already exists for this standard dose, the selection of this dose also allows us to use existing data to inform strategies for safety and tolerability monitoring to minimize risk, as detailed in the study design. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Provision of signed and dated informed consent form
- Stated willingness and ability to comply with all study procedures and availability for the duration of the study
- Age: 18+
- Established diagnosis of multiple sclerosis
- Evidence of Epstein Barr virus (EBV) infection by serological testing for EBV antibodies antibodies (subjects will have EBV testing performed at the pre-screening visit and if serologies are negative, the subjects will be removed from the study)
Key exclusion criteria (13 listed)
- Pregnancy or lactation
- Known allergic reactions to components of Truvada
- Previous treatment with Truvada or Descovy
- Unknown HIV status (subjects must have completed HIV antigen/antibody and viral load testing within the prior 6 months to being enrolled or have the testing completed at the pre-screening visit)
- Active or latent hepatitis B (HBV) (subjects must have completed HBV serologies - HbsAg, anti-HBs, and anti-HBc - within the prior 6 months to being enrolled or have the testing completed at the pre-screening visit)
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 |
|---|---|---|
| Truvada (tenofovir/emtricitabine)Also: TDFDoses and route of administration of the study drug will be kept the same as for the FDA-approved indication of HIV-1 prevention in healthy individuals. The study drug is not FDA-approved for the treatment of multiple sclerosis. | Drug | Treatment arm |
Primary outcome
Epstein Barr virus (EBV) viral load
Time frame: Change from baseline at three months
EBV viral load will be quantified in saliva and peripheral blood using a sensitive assay.
2 secondary outcomes
Tolerability of Truvada (tenofovir/emtricitabine)
Time frame: Change from baseline at three months
Fatigue
Time frame: Change from baseline at three months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
- Individual participant dataSharing planned: No
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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.
Michael Levy, MD, PhD principal investigator
Massachusetts General Hospital
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 Truvada (tenofovir/emtricitabine) in people with Multiple Sclerosis, run by Massachusetts General Hospital 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 5 inclusion and 13 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: enrolling by invitation, as of the sponsor's last update on 14 Jul 2026. 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?
This study is still under way. Results are not available in the source record yet.
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?
Epstein Barr virus (EBV) viral load (time frame: Change from baseline at three months). 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 14 Jul 2026.