Post Treatment Lyme Syndrome (PTLS)PTLSNCT02687165
Uncovering Neural and Immune Mechanisms of Chronic Pain in Post Treatment Lyme Syndrome
A study testing Milnacipran and D-cycloserine in people with Post Treatment Lyme Syndrome (PTLS) and Chronic Pain, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
This study will investigate (a) neural and immune mechanisms underlying chronic pain in PTLS by comparing a group of PTLS patients and healthy participants on brain imaging, sensory, and immune markers; and (b) assess change in pain, brain imaging (fMRI and MRS), sensory, and immune markers in response to a… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Post Treatment Lyme Syndrome (PTLS), Chronic Pain
- What is being tested?
- Milnacipran and D-cycloserine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jan 2016to 16 Jan 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- History of Lyme Disease and treatment:
- Current chronic pain in the musculoskeletal system
- clinically troubling sensory hypersensitivity (e.g., light or touch)
- Able to speak and read English
- Willing to not take other than study centrally acting pharmacologic agents prior to MRI and for the duration of treatment with study medications
Who cannot join
- Diagnosis of another (not LYME) general medical condition that has a major role in the onset, severity, exacerbation or maintenance of pain, or sensory hypersensitivity.
- DSM-IV Axis I lifetime diagnosis of Pervasive Developmental Disorder, Autism, Psychotic disorder, Bipolar Disorder, Substance dependence.
- I current diagnosis of Major Depressive Disorder or substance abuse
- History of head injury with loss of consciousness (>5min), neurologic disease, seizures (excluding febrile seizures) or serious unstable medical condition (e.g. cancer, diabetes)
- Current or recent (last month) opiate use
- For 2 weeks prior to MRI and diagnostic visit, unable to be free of centrally active medications or treatment methods. These include medications commonly used to treat pain (eg, antidepressants, muscle relaxants, centrallyacting analgesics), as well as transcutaneous electrical nerve stimulation, biofeedback, tender and trigger point injections, acupuncture, and anesthetic or narcotic patches. PRN doses of short acting medications, e.g. acetaminophen, aspirin, and nonsteroidal antiinflammatory agents will be allowed for pain with usage carefully monitored, but patients must be willing to be off of these medications for 24 hours prior to the major evaluations at intake and MRI study visit. Stable doses of non-benzodiazepines will be allowed for sleep (but not tricyclics)
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- Ferromagnetic implants (e.g. pacemaker, etc.)
- Metal Braces or Retainers
- Transdermal medicinal patches that cannot be removed
- Birth at < 37 weeks gestational age (prior studies have shown dramatic effects on brain structure and function in prematurely born children)
- Claustrophobia
- Women will be excluded if they are pregnant, lactating, or not either surgically-sterile or using appropriate methods of birth control. Women must agree to continue using applicable birth control throughout the trial. All women of child-bearing potential must have a negative pregnancy test at the intake visit.
- Inability to reliably rate intensity of pain in response to a fixed thermal stimulus
- Inability to tolerate sound intensity of fMRI
- Individuals currently successfully treated by medications for their pain.
- History of inability to tolerate treatment with SSRI or SNRI medications or d-cycloserine; or medication induced mania
- Renal insufficiency or congestive heart failure
- Hepatic malfunction Liver Test
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032-0000
About this study
This study will investigate (a) neural and immune mechanisms underlying chronic pain in PTLS by comparing a group of PTLS patients and healthy participants on brain imaging, sensory, and immune markers; and (b) assess change in pain, brain imaging (fMRI and MRS), sensory, and immune markers in response to a combination of SNRI and glutamatergic treatment for chronic pain in PTLS (Milnacipran and D-cycloserine).
Read the detailed description
At least 5-15% of patients with Lyme disease (7,500-45,000 new cases a year) develop Post-treatment Lyme Syndrome (PTLS) - debilitating residual symptoms that last months to years, even after having received antibiotic treatment. Often patients with PTLS experience chronic pain in their muscles or joints or nerves.
Because many PTLS patients have pain that persists despite antibiotics and because we know that medicines which modulate the pain pathways in the brain can help to reduce or eliminate pain, we plan to treat patients with a medicine that is FDA approved for the treatment of pain. This medicine is known as Milnacipran (the trade name is "Savella"); this medicine is not addictive and it has been shown to reduce chronic pain by its multiple actions on pain pathways. All patients in the study will be treated with this FDA approved medicine.
Second, we wish to test whether the pain can be improved even further by adding a medicine which is known to modulate the glutamate transmission involved with pain in the brain. This medicine - D-Cycloserine - is actually an antibiotic, currently FDA approved for the treatment of tuberculosis. Because of its action on glutamate receptors, we are hypothesizing that it will help to decrease pain even further in patients with Lyme-related pain. In order to test this hypothesis, after 6 weeks of being on Milnacipran, all patients will then be given an additional treatment - either D-Cycloserine or a placebo pill (a placebo is a pill that does not contain any active medication.) At the end of 12 weeks, we will then evaluate improvement compared to when the patient started in the study using the same clinical and neuroimaging (fMRI) tests.
Finally, we want to know whether patients with PTLS have over-active central pain circuits in the brain. Because pain is processed through the brain's pain circuits, we wish to examine whether people suffering from PTLS have hyper-active pain circuits that make them more sensitive to pain than those who have normally-active pain circuits. To do this, we will be comparing patients with PTLS to healthy volunteers by conducting careful neurologic and brain imaging (fMRI) studies.
We hope that this study will provide valuable information about how the brain processes pain signals in PTLS and about whether this treatment approach is effective.
- Conditions
- Post Treatment Lyme Syndrome (PTLS), Chronic Pain
- Being tested
- Milnacipran and D-cycloserine
- Medical subject headings
- Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Milnacipran and D-cycloserineDrug
Milnacipran augmented by D-cycloserine
| Study group | Role | What they receive |
|---|---|---|
| Milnacipran augmented by D-cycloserine | Active comparator | participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving D-cycloserine in addition to Milnacipran Receives: Drug: Milnacipran and D-cycloserine |
| Milnacipran augmented by Placebo | Placebo comparator | participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving placebo in addition to Milnacipran Receives: Drug: Milnacipran and D-cycloserine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brief Pain Inventory
average pain over past week on the scale from 0-10. Data were not collected.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2016 (estimated)
- Study start16 Jan 2016
- Primary completion16 Jan 2017
- Study completion16 Jan 2017
Why it stopped: Slow recruitment due to strict inclusion/exclusion criteria
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Post Treatment Lyme Syndrome (PTLS)Studies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alla Landa, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02687165
- Sponsor's protocol ID
- 7003
- Acronym
- PTLS
- Status last verified
- May 2020
- First submitted
- 16 Feb 2016
- Last updated
- 1 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Uncovering Neural and Immune Mechanisms of Chronic Pain in Post Treatment Lyme Syndrome
- ClinicalTrials.gov ID
- NCT02687165
- Acronym / sponsor ID
- PTLS / 7003
- Conditions
- Post Treatment Lyme Syndrome (PTLS), Chronic Pain
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment due to strict inclusion/exclusion criteria
- Enrolment
- 4 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Study start
- 16 Jan 2016 (actual)
- Primary completion
- 16 Jan 2017 (actual)
- Study completion
- 16 Jan 2017 (actual)
- First posted
- 22 Feb 2016 (estimated)
- Results
- Posted 1 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate (a) neural and immune mechanisms underlying chronic pain in PTLS by comparing a group of PTLS patients and healthy participants on brain imaging, sensory, and immune markers; and (b) assess change in pain, brain imaging (fMRI and MRS), sensory, and immune markers in response to a combination of SNRI and glutamatergic treatment for chronic pain in PTLS (Milnacipran and D-cycloserine).
Detailed description
At least 5-15% of patients with Lyme disease (7,500-45,000 new cases a year) develop Post-treatment Lyme Syndrome (PTLS) - debilitating residual symptoms that last months to years, even after having received antibiotic treatment. Often patients with PTLS experience chronic pain in their muscles or joints or nerves.
Because many PTLS patients have pain that persists despite antibiotics and because we know that medicines which modulate the pain pathways in the brain can help to reduce or eliminate pain, we plan to treat patients with a medicine that is FDA approved for the treatment of pain. This medicine is known as Milnacipran (the trade name is "Savella"); this medicine is not addictive and it has been shown to reduce chronic pain by its multiple actions on pain pathways. All patients in the study will be treated with this FDA approved medicine.
Second, we wish to test whether the pain can be improved even further by adding a medicine which is known to modulate the glutamate transmission involved with pain in the brain. This medicine - D-Cycloserine - is actually an antibiotic, currently FDA approved for the treatment of tuberculosis. Because of its action on glutamate receptors, we are hypothesizing that it will help to decrease pain even further in patients with Lyme-related pain. In order to test this hypothesis, after 6 weeks of being on Milnacipran, all patients will then be given an additional treatment - either D-Cycloserine or a placebo pill (a placebo is a pill that does not contain any active medication.) At the end of 12 weeks, we will then evaluate improvement compared to when the patient started in the study using the same clinical and neuroimaging (fMRI) tests.
Finally, we want to know whether patients with PTLS have over-active central pain circuits in the brain. Because pain is processed through the brain's pain circuits, we wish to examine whether people suffering from PTLS have hyper-active pain circuits that make them more sensitive to pain than those who have normally-active pain circuits. To do this, we will be comparing patients with PTLS to healthy volunteers by conducting careful neurologic and brain imaging (fMRI) studies.
We hope that this study will provide valuable information about how the brain processes pain signals in PTLS and about whether this treatment approach is effective.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Milnacipran augmented by D-cycloserine | Active comparator | Drug: Milnacipran and D-cycloserineparticipants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving D-cycloserine in addition to Milnacipran |
| Milnacipran augmented by Placebo | Placebo comparator | Drug: Milnacipran and D-cycloserineparticipants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving placebo in addition to Milnacipran |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- History of Lyme Disease and treatment:
- Current chronic pain in the musculoskeletal system
- clinically troubling sensory hypersensitivity (e.g., light or touch)
- Able to speak and read English
- Willing to not take other than study centrally acting pharmacologic agents prior to MRI and for the duration of treatment with study medications
Key exclusion criteria (18 listed)
- Diagnosis of another (not LYME) general medical condition that has a major role in the onset, severity, exacerbation or maintenance of pain, or sensory hypersensitivity.
- DSM-IV Axis I lifetime diagnosis of Pervasive Developmental Disorder, Autism, Psychotic disorder, Bipolar Disorder, Substance dependence.
- I current diagnosis of Major Depressive Disorder or substance abuse
- History of head injury with loss of consciousness (>5min), neurologic disease, seizures (excluding febrile seizures) or serious unstable medical condition (e.g. cancer, diabetes)
- Current or recent (last month) opiate use
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 |
|---|---|---|
| Milnacipran and D-cycloserineMilnacipran augmented by D-cycloserine | Drug | Milnacipran augmented by D-cycloserine, Milnacipran augmented by Placebo |
Primary outcome
Brief Pain Inventory
Time frame: 12 weeks
average pain over past week on the scale from 0-10. Data were not collected.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Milnacipran and D-cycloserine in people with Post Treatment Lyme Syndrome (PTLS) and Chronic Pain, run by New York State Psychiatric Institute 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 18 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: stopped early, as of the sponsor's last update on 1 Jun 2020. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Brief Pain Inventory (time frame: 12 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 1 Jun 2020.