Chronic Pain, Post Treatment Lyme Syndrome (PTLS)
Conditions
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.
Interventions
DRUGMilnacipran and D-cycloserine
Milnacipran augmented by D-cycloserine
Sponsors
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brief Pain Inventory | 12 weeks | average pain over past week on the scale from 0-10. Data were not collected. |
Countries
United States
Participant flow
Recruitment details
4 patients were screened, but none was randomized
Pre-assignment details
4 patients were screened, but no one was randomized
Participants by arm
| Arm | Count |
|---|---|
| All Participants participants were not randomized. reporting all subjects together. | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 46.5 years STANDARD_DEVIATION 11.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Brief Pain Inventory
average pain over past week on the scale from 0-10. Data were not collected.
Time frame: 12 weeks
Population: patients didn't compete the study. Data were not collected.