Post-Treatment Lyme DiseasePhase 2T-4NCT05219929
Tetracycline Treatment Tolerability Trial
A Phase 2 study testing Tetracycline 500 Mg in people with Post-Treatment Lyme Disease, run by Johns Hopkins University at 1 site in United States.
Trial summary
Randomized, double-blind, placebo-controlled study (with a one-week washout period) where subjects receive either 3 months of tetracycline or 3 months of placebo. After the 3 month primary endpoint, in the follow-up period, patients will be assigned to the alternate treatment for 3 months with blind maintained. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Post-Treatment Lyme Disease
- What is being tested?
- Tetracycline 500 Mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Nov 2022to 9 Jun 2026
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 18 to 80 years of age
- Meet criteria operationalized from the Infectious Diseases Society of America (IDSA) case definition for PTLD (ref) previously treated with at least one recommended course of antibiotic therapy.
- Have persistent symptoms in at least the last month. "Currently have at least one symptom attributed to Lyme disease that a) you've experienced in the past month and b) limits your daily functioning at least half the time when its present"
- Fatigue Severity Scale survey score of at least 4.0 signifying moderate or greater severity of fatigue.
- Medical Records documented history of definite or probable Lyme disease with onset starts in the last 5 years, with symptoms developing within 1 year of Lyme onset.
- Definite LD. Medical record documented history of erythema migrans or medical record documented history of a Lyme disease compatible neurologic, cardiac or musculoskeletal manifestation of Lyme disease with a confirmatory 2-tier serology, modified 2-tier serologic test, or immunoglobulin G (IgG) western blot and a lack of alternative diagnosis Probable LD. Medical record documented history of Lyme disease with atypical or nonspecific manifestations with a confirmatory 2-tier serology, modified 2-tier serologic test, or IgG western blot and a lack of alternative diagnosis.
Who cannot join
- Medications:
- No antibiotics in the prior 2 months No change in medications during the prior 4 months that might have an impact on primary and secondary outcome measures. See list. No immunosuppressive medications No medications that interact with tetracycline: atovaquone, retinoid medications taken by mouth (such as acitretin, isotretinoin), strontium, digoxin, kaolin pectin, warfarin Use of prescription or over the counter (OTC) medications containing calcium (i.e. Tums)
- History of the following conditions predating the diagnosis of Lyme disease: Myalgic encephalomyelitis/chronic fatigue syndrome Fibromyalgia Autoimmune disease
- Major psychiatric conditions Bipolar disorder, delusional disorder, schizophrenia Major depression Suicidal ideation with intent during the prior 6 months
- History of the following conditions in the last 4 months Alcohol or substance abuse Cancer (other than skin) Untreated HIV/AIDS Untreated moderate to severe sleep apnea Hepatitis A, B or C Pregnancy or intent to become pregnant Breastfeeding
- BMI greater than 40
- Other conditions at the discretion of the clinician
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins Lyme Disease Research Center
Lutherville, Maryland, 21093
About this study
Official title: T4 - Tetracycline Treatment Tolerability Trial A Pilot Study Examining the Feasibility and Tolerability of Tetracycline Therapy in Post-Treatment Lyme Disease (PTLD)
Randomized, double-blind, placebo-controlled study (with a one-week washout period) where subjects receive either 3 months of tetracycline or 3 months of placebo. After the 3 month primary endpoint, in the follow-up period, patients will be assigned to the alternate treatment for 3 months with blind maintained.
Read the detailed description
There is precedent for the use of tetracycline class antibiotics as an anti-inflammatory agent in chronic illnesses including dermatologic and rheumatologic illnesses. The 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis (RA) includes long-term therapy with tetracycline in its treatment recommendations. This class of antibiotics has known anti-inflammatory effect in addition to its antimicrobial properties. Tetracyclines, in particular minocycline, have been associated with a significant improvement in disease activity in RA with no increased risk of adverse effects.
To date, no clinical trials have examined the benefit of extended duration; i.e. >4 weeks tetracycline therapy in PTLD. Concerns over side effects and the development of antibiotic-resistance and superinfections such as Clostridioides difficile have limited the use of long-term antibiotics, including tetracycline. There is a large body of literature on tetracycline and other drugs in this class regarding the drugs' anti-inflammatory properties and potential benefit in several non-infectious diseases such cerebrovascular disease, rheumatoid arthritis, and rosacea.
The investigators believe that this deserves further study. Initially, the investigators propose this pilot study to examine the feasibility and tolerability of tetracycline treatment in PTLD Secondarily, the investigators propose to assess preliminary data on the efficacy of 3 months duration tetracycline treatment in reducing PTLD symptoms at (1) the end of the three-month treatment period, and (2) rate of change during the 1st 3 months of treatment.
Lastly, as an exploration, the investigators will explore in the follow-up period the return of symptoms after the completion of the 3 month tetracycline and the effect of 3 months of tetracycline in the placebo arm.
The investigators hypothesize that a tetracycline study over a 4 year interval will be feasible to conduct and tolerable to patients. Secondarily, the investigators hypothesize that 3 months of tetracycline treatment will be associated with greater improvements in fatigue, symptom burden and functional impact than placebo. This research is important because the long-term sequelae of LD are debilitating to patients and costly to society.
- Conditions
- Post-Treatment Lyme Disease
- Being tested
- Tetracycline 500 Mg, Placebo
- Medical subject headings
- Post-Lyme Disease Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tetracycline 500 MgDrug
500 mg three times daily
PlaceboOther
Placebo for Tetracycline given same way as Tetracycline.
| Study group | Role | What they receive |
|---|---|---|
| Tetracycline First | Active comparator | Tetracycline for first 3 months, placebo for second 3 months. Receives: Drug: Tetracycline 500 Mg; Other: Placebo |
| Placebo First | Placebo comparator | Placebo for first 3 months, tetracycline for second 3 months. Receives: Drug: Tetracycline 500 Mg; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participant Retention
Number of participants retained.
Measured: 36 months
Tolerability as assessed by number of side effects
Tolerability as assessed by number of side effects, as measured by Systematic Assessment for Treatment Emergent Events (SAFTEE).
Measured: 36 months
Tolerability as assessed by severity of side effects
Tolerability as assessed by severity of side effects, as measured by SAFTEE.
Measured: 36 months
Secondary outcomes (1)
Fatigue as assessed by the Fatigue Severity Scale
A change of 0.7 in the Fatigue Severity Scale will be considered clinically significant
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2022
- Study start2 Nov 2022
- Primary completion9 Jun 2026
- Study completion9 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-Treatment Lyme DiseaseStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Steve and Alexandra Cohen Foundation
- Responsible party
- Sponsor
- Investigators
- John N. Aucott, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05219929
- Sponsor's protocol ID
- IRB00288079
- Acronym
- T-4
- Status last verified
- Sep 2026
- First submitted
- 21 Jan 2022
- Last updated
- 28 Sep 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 28 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T4 - Tetracycline Treatment Tolerability Trial A Pilot Study Examining the Feasibility and Tolerability of Tetracycline Therapy in Post-Treatment Lyme Disease (PTLD)
- ClinicalTrials.gov ID
- NCT05219929
- Acronym / sponsor ID
- T-4 / IRB00288079
- Conditions
- Post-Treatment Lyme Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Steve and Alexandra Cohen Foundation
- Study start
- 2 Nov 2022 (actual)
- Primary completion
- 9 Jun 2026 (actual)
- Study completion
- 9 Jun 2026 (actual)
- First posted
- 2 Feb 2022 (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.
Randomized, double-blind, placebo-controlled study (with a one-week washout period) where subjects receive either 3 months of tetracycline or 3 months of placebo. After the 3 month primary endpoint, in the follow-up period, patients will be assigned to the alternate treatment for 3 months with blind maintained.
Detailed description
There is precedent for the use of tetracycline class antibiotics as an anti-inflammatory agent in chronic illnesses including dermatologic and rheumatologic illnesses. The 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis (RA) includes long-term therapy with tetracycline in its treatment recommendations. This class of antibiotics has known anti-inflammatory effect in addition to its antimicrobial properties. Tetracyclines, in particular minocycline, have been associated with a significant improvement in disease activity in RA with no increased risk of adverse effects.
To date, no clinical trials have examined the benefit of extended duration; i.e. >4 weeks tetracycline therapy in PTLD. Concerns over side effects and the development of antibiotic-resistance and superinfections such as Clostridioides difficile have limited the use of long-term antibiotics, including tetracycline. There is a large body of literature on tetracycline and other drugs in this class regarding the drugs' anti-inflammatory properties and potential benefit in several non-infectious diseases such cerebrovascular disease, rheumatoid arthritis, and rosacea.
The investigators believe that this deserves further study. Initially, the investigators propose this pilot study to examine the feasibility and tolerability of tetracycline treatment in PTLD Secondarily, the investigators propose to assess preliminary data on the efficacy of 3 months duration tetracycline treatment in reducing PTLD symptoms at (1) the end of the three-month treatment period, and (2) rate of change during the 1st 3 months of treatment.
Lastly, as an exploration, the investigators will explore in the follow-up period the return of symptoms after the completion of the 3 month tetracycline and the effect of 3 months of tetracycline in the placebo arm.
The investigators hypothesize that a tetracycline study over a 4 year interval will be feasible to conduct and tolerable to patients. Secondarily, the investigators hypothesize that 3 months of tetracycline treatment will be associated with greater improvements in fatigue, symptom burden and functional impact than placebo. This research is important because the long-term sequelae of LD are debilitating to patients and costly to society.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tetracycline First | Active comparator | Drug: Tetracycline 500 Mg, Other: PlaceboTetracycline for first 3 months, placebo for second 3 months. |
| Placebo First | Placebo comparator | Drug: Tetracycline 500 Mg, Other: PlaceboPlacebo for first 3 months, tetracycline for second 3 months. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- ≥ 18 to 80 years of age
- Meet criteria operationalized from the Infectious Diseases Society of America (IDSA) case definition for PTLD (ref) previously treated with at least one recommended course of antibiotic therapy.
- Have persistent symptoms in at least the last month. "Currently have at least one symptom attributed to Lyme disease that a) you've experienced in the past month and b) limits your daily functioning at least half the time when its present"
- Fatigue Severity Scale survey score of at least 4.0 signifying moderate or greater severity of fatigue.
- Medical Records documented history of definite or probable Lyme disease with onset starts in the last 5 years, with symptoms developing within 1 year of Lyme onset.
Key exclusion criteria (7 listed)
- Medications:
- No antibiotics in the prior 2 months No change in medications during the prior 4 months that might have an impact on primary and secondary outcome measures. See list. No immunosuppressive medications No medications that interact with tetracycline: atovaquone, retinoid medications taken by mouth (such as acitretin, isotretinoin), strontium, digoxin, kaolin pectin, warfarin Use of prescription or over the counter (OTC) medications containing calcium (i.e. Tums)
- History of the following conditions predating the diagnosis of Lyme disease: Myalgic encephalomyelitis/chronic fatigue syndrome Fibromyalgia Autoimmune disease
- Major psychiatric conditions Bipolar disorder, delusional disorder, schizophrenia Major depression Suicidal ideation with intent during the prior 6 months
- History of the following conditions in the last 4 months Alcohol or substance abuse Cancer (other than skin) Untreated HIV/AIDS Untreated moderate to severe sleep apnea Hepatitis A, B or C Pregnancy or intent to become pregnant Breastfeeding
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 |
|---|---|---|
| Tetracycline 500 Mg500 mg three times daily | Drug | Placebo First, Tetracycline First |
| PlaceboPlacebo for Tetracycline given same way as Tetracycline. | Other | Placebo First, Tetracycline First |
Primary outcome
Participant Retention
Time frame: 36 months
Number of participants retained.
Tolerability as assessed by number of side effects
Time frame: 36 months
Tolerability as assessed by number of side effects, as measured by Systematic Assessment for Treatment Emergent Events (SAFTEE).
Tolerability as assessed by severity of side effects
Time frame: 36 months
Tolerability as assessed by severity of side effects, as measured by SAFTEE.
1 secondary outcome
Fatigue as assessed by the Fatigue Severity Scale
Time frame: 36 months
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 28 Sep 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. This study is not recruiting at the moment.
John N. Aucott, MD principal investigator
Johns Hopkins University
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 Tetracycline 500 Mg in people with Post-Treatment Lyme Disease, run by Johns Hopkins University 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 6 inclusion and 7 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 28 Sep 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. Some participants in this study may receive a placebo. 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?
Participant Retention (time frame: 36 months). The study lists 3 primary outcomes in all. 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 28 Sep 2026.