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

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02687165
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arms: 2
• Actual Duration (Months): 12
• Patients Per Site Per Month: 0.3

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Post Treatment Lyme Syndrome (PTLS); Chronic Pain	Drug: Milnacipran and D-cycloserine	N/A

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

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Uncovering Neural and Immune Mechanisms of Chronic Pain in Post Treatment Lyme Syndrome
• Actual Study Start Date: Jan 16, 2016
• Actual Primary Completion Date: Jan 16, 2017
• Actual Study Completion Date: Jan 16, 2017

Arms and Interventions

Arm	Intervention/Treatment
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	Drug: Milnacipran and D-cycloserine; Milnacipran augmented by 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	Drug: Milnacipran and D-cycloserine; Milnacipran augmented by D-cycloserine

Outcome Measures

Primary Outcome Measures

1. Brief Pain Inventory [12 weeks]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia University Medical Center	New York	New York	United States	10032-0000

Sponsors and Collaborators

• New York State Psychiatric Institute

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alla Landa, Assistant Professor, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT05055622
• Other Study ID Numbers: 7003; NCT05055622
• First Posted: Feb 22, 2016
• Last Update Posted: Jun 1, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Syndrome; Chronic Pain; Cycloserine; Milnacipran; Levomilnacipran

Study Results

Participant Flow

Recruitment Details	4 patients were screened, but none was randomized
Pre-assignment Detail	4 patients were screened, but no one was randomized

Arm/Group Title	Milnacipran Augmented by D-cycloserine	Milnacipran Augmented by Placebo
Arm/Group Description	participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving D-cycloserine in addition to Milnacipran Milnacipran and D-cycloserine: Milnacipran augmented by D-cycloserine	participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving placebo in addition to Milnacipran Milnacipran and D-cycloserine: Milnacipran augmented by D-cycloserine
Period Title: Overall Study
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	participants were not randomized. reporting all subjects together.
Overall Participants	4
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.5 (11.7)
Sex: Female, Male (Count of Participants)
Female	2 50%
Male	2 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	4 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Brief Pain Inventory
Description	average pain over past week on the scale from 0-10. Data were not collected.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

patients didn't compete the study. Data were not collected.

Arm/Group Title	Milnacipran Augmented by D-cycloserine	Milnacipran Augmented by Placebo
Arm/Group Description	participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving D-cycloserine in addition to Milnacipran Milnacipran and D-cycloserine: Milnacipran augmented by D-cycloserine	participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving placebo in addition to Milnacipran Milnacipran and D-cycloserine: Milnacipran augmented by D-cycloserine
Measure Participants	0	0

Adverse Events

Time Frame	Only some baseline demographic information were collected. And no subject was randomized. Study terminated.
Adverse Event Reporting Description	Adverse events were not monitored/assessed. 0 Participants at Risk.
Arm/Group Title	Milnacipran Augmented by D-cycloserine		Milnacipran Augmented by Placebo
Arm/Group Description	participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving D-cycloserine in addition to Milnacipran Milnacipran and D-cycloserine: Milnacipran augmented by D-cycloserine		participants will be receiving Milnacipran for 12 weeks. During weeks 6-12 participants will be receiving placebo in addition to Milnacipran Milnacipran and D-cycloserine: Milnacipran augmented by D-cycloserine
All Cause Mortality
	Milnacipran Augmented by D-cycloserine		Milnacipran Augmented by Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Milnacipran Augmented by D-cycloserine		Milnacipran Augmented by Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Milnacipran Augmented by D-cycloserine		Milnacipran Augmented by Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.