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Tetracycline Treatment Tolerability Trial (T-4)

Primary Purpose

Post-Treatment Lyme Disease

Status

Enrolling by invitation

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Tetracycline 500 Mg

Placebo

About this trial

This is an interventional other trial for Post-Treatment Lyme Disease

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

≥ 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.

Exclusion Criteria:

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

Sites / Locations

Johns Hopkins Lyme Disease Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Tetracycline First

Placebo First

Arm Description

Tetracycline for first 3 months, placebo for second 3 months.

Placebo for first 3 months, tetracycline for second 3 months.

Outcomes

Primary Outcome Measures

Participant Retention

Number of participants retained.

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).

Tolerability as assessed by severity of side effects

Tolerability as assessed by severity of side effects, as measured by SAFTEE.

Secondary Outcome Measures

Fatigue as assessed by the Fatigue Severity Scale

A change of 0.7 in the Fatigue Severity Scale will be considered clinically significant

Full Information

NCT ID

NCT05219929

First Posted

January 21, 2022

Last Updated

June 23, 2023

Sponsor

Johns Hopkins University

1. Study Identification

Unique Protocol Identification Number

NCT05219929

Brief Title

Tetracycline Treatment Tolerability Trial

Acronym

T-4

Official Title

T4 - Tetracycline Treatment Tolerability Trial A Pilot Study Examining the Feasibility and Tolerability of Tetracycline Therapy in Post-Treatment Lyme Disease (PTLD)

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Enrolling by invitation

Study Start Date

November 2, 2022 (Actual)

Primary Completion Date

October 2024 (Anticipated)

Study Completion Date

October 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Johns Hopkins University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Post-Treatment Lyme Disease

7. Study Design

Primary Purpose

Other

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Tetracycline First

Arm Type

Active Comparator

Arm Description

Tetracycline for first 3 months, placebo for second 3 months.

Arm Title

Placebo First

Arm Type

Placebo Comparator

Arm Description

Placebo for first 3 months, tetracycline for second 3 months.

Intervention Type

Drug

Intervention Name(s)

Tetracycline 500 Mg

Intervention Description

500 mg three times daily

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Placebo for Tetracycline given same way as Tetracycline.

Primary Outcome Measure Information:

Title

Participant Retention

Description

Number of participants retained.

Time Frame

36 months

Title

Tolerability as assessed by number of side effects

Description

Tolerability as assessed by number of side effects, as measured by Systematic Assessment for Treatment Emergent Events (SAFTEE).

Time Frame

36 months

Title

Tolerability as assessed by severity of side effects

Description

Tolerability as assessed by severity of side effects, as measured by SAFTEE.

Time Frame

36 months

Secondary Outcome Measure Information:

Title

Fatigue as assessed by the Fatigue Severity Scale

Description

A change of 0.7 in the Fatigue Severity Scale will be considered clinically significant

Time Frame

36 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: ≥ 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. Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John N. Aucott, MD

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Johns Hopkins Lyme Disease Research Center

City

Lutherville

State/Province

Maryland

ZIP/Postal Code

21093

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Tetracycline Treatment Tolerability Trial

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