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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02687165
Recruitment Status : Terminated (Slow recruitment due to strict inclusion/exclusion criteria)
First Posted : February 22, 2016
Results First Posted : June 1, 2020
Last Update Posted : June 1, 2020
Sponsor:
Information provided by (Responsible Party):
Alla Landa, New York State Psychiatric Institute

Tracking Information
First Submitted Date  ICMJE February 16, 2016
First Posted Date  ICMJE February 22, 2016
Results First Submitted Date  ICMJE February 1, 2020
Results First Posted Date  ICMJE June 1, 2020
Last Update Posted Date June 1, 2020
Actual Study Start Date  ICMJE January 16, 2016
Actual Primary Completion Date January 16, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 18, 2020)
Brief Pain Inventory [ Time Frame: 12 weeks ]
average pain over past week on the scale from 0-10. Data were not collected.
Original Primary Outcome Measures  ICMJE
 (submitted: February 19, 2016)
Pain [ Time Frame: 1 week ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Uncovering Neural and Immune Mechanisms of Chronic Pain in Post Treatment Lyme Syndrome
Official Title  ICMJE Uncovering Neural and Immune Mechanisms of Chronic Pain in Post Treatment Lyme Syndrome
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Post Treatment Lyme Syndrome (PTLS)
  • Chronic Pain
Intervention  ICMJE Drug: Milnacipran and D-cycloserine
Milnacipran augmented by D-cycloserine
Study Arms  ICMJE
  • Active Comparator: Milnacipran augmented by D-cycloserine
    participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving D-cycloserine in addition to Milnacipran
    Intervention: Drug: Milnacipran and D-cycloserine
  • Placebo Comparator: Milnacipran augmented by Placebo
    participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving placebo in addition to Milnacipran
    Intervention: Drug: Milnacipran and D-cycloserine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: May 18, 2020)
4
Original Estimated Enrollment  ICMJE
 (submitted: February 19, 2016)
40
Actual Study Completion Date  ICMJE January 16, 2017
Actual Primary Completion Date January 16, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02687165
Other Study ID Numbers  ICMJE 7003
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Alla Landa, New York State Psychiatric Institute
Study Sponsor  ICMJE New York State Psychiatric Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account New York State Psychiatric Institute
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP