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Uncovering Neural and Immune Mechanisms of Chronic Pain in Post Treatment Lyme Syndrome (PTLS)

Primary Purpose

Post Treatment Lyme Syndrome (PTLS), Chronic Pain

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Milnacipran and D-cycloserine
Sponsored by
New York State Psychiatric Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Post Treatment Lyme Syndrome (PTLS)

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. History of Lyme Disease and treatment:
  2. Current chronic pain in the musculoskeletal system
  3. clinically troubling sensory hypersensitivity (e.g., light or touch)
  4. Able to speak and read English
  5. Willing to not take other than study centrally acting pharmacologic agents prior to MRI and for the duration of treatment with study medications

Exclusion Criteria:

  1. 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.
  2. DSM-IV Axis I lifetime diagnosis of Pervasive Developmental Disorder, Autism, Psychotic disorder, Bipolar Disorder, Substance dependence.
  3. I current diagnosis of Major Depressive Disorder or substance abuse
  4. History of head injury with loss of consciousness (>5min), neurologic disease, seizures (excluding febrile seizures) or serious unstable medical condition (e.g. cancer, diabetes)
  5. Current or recent (last month) opiate use
  6. 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)
  7. Ferromagnetic implants (e.g. pacemaker, etc.)
  8. Metal Braces or Retainers
  9. Transdermal medicinal patches that cannot be removed
  10. Birth at < 37 weeks gestational age (prior studies have shown dramatic effects on brain structure and function in prematurely born children)
  11. Claustrophobia
  12. 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.
  13. Inability to reliably rate intensity of pain in response to a fixed thermal stimulus
  14. Inability to tolerate sound intensity of fMRI
  15. Individuals currently successfully treated by medications for their pain.
  16. History of inability to tolerate treatment with SSRI or SNRI medications or d-cycloserine; or medication induced mania
  17. Renal insufficiency or congestive heart failure
  18. Hepatic malfunction Liver Test

Sites / Locations

  • Columbia University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Milnacipran augmented by D-cycloserine

Milnacipran augmented by Placebo

Arm Description

participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving D-cycloserine in addition to Milnacipran

participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving placebo in addition to Milnacipran

Outcomes

Primary Outcome Measures

Brief Pain Inventory
average pain over past week on the scale from 0-10. Data were not collected.

Secondary Outcome Measures

Full Information

First Posted
February 16, 2016
Last Updated
May 18, 2020
Sponsor
New York State Psychiatric Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02687165
Brief Title
Uncovering Neural and Immune Mechanisms of Chronic Pain in Post Treatment Lyme Syndrome
Acronym
PTLS
Official Title
Uncovering Neural and Immune Mechanisms of Chronic Pain in Post Treatment Lyme Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
May 2020
Overall Recruitment Status
Terminated
Why Stopped
Slow recruitment due to strict inclusion/exclusion criteria
Study Start Date
January 16, 2016 (Actual)
Primary Completion Date
January 16, 2017 (Actual)
Study Completion Date
January 16, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York State Psychiatric Institute

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post Treatment Lyme Syndrome (PTLS), Chronic Pain

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Milnacipran augmented by D-cycloserine
Arm Type
Active Comparator
Arm Description
participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving D-cycloserine in addition to Milnacipran
Arm Title
Milnacipran augmented by Placebo
Arm Type
Placebo Comparator
Arm Description
participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving placebo in addition to Milnacipran
Intervention Type
Drug
Intervention Name(s)
Milnacipran and D-cycloserine
Intervention Description
Milnacipran augmented by D-cycloserine
Primary Outcome Measure Information:
Title
Brief Pain Inventory
Description
average pain over past week on the scale from 0-10. Data were not collected.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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) 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
Facility Information:
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032-0000
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Uncovering Neural and Immune Mechanisms of Chronic Pain in Post Treatment Lyme Syndrome

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