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D-cycloserine for the Treatment of Chronic, Refractory Low Back Pain

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ClinicalTrials.gov Identifier: NCT03535688
Recruitment Status : Recruiting
First Posted : May 24, 2018
Last Update Posted : May 24, 2018
Sponsor:
Collaborator:
United States Department of Defense
Information provided by (Responsible Party):
Thomas J. Schnitzer, Northwestern University

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of D-cycloserine versus placebo in relieving the signs and symptoms of patients with chronic lower back pain.

Condition or disease Intervention/treatment Phase
Low Back Pain Pain Drug: D-cycloserine Drug: Placebo Phase 3

Detailed Description:
This is a 26-week, double-blind, randomized, placebo-controlled two-arm parallel-group trial of d-cycloserine, a pharmacological treatment selected based on positive results from previous preclinical and clinical studies, for the treatment of chronic, refractory low back pain (CBP). After a 2-week screening period, individuals will be randomized to receive either 12 weeks of d-cycloserine or placebo and then followed for an additional 12 weeks to evaluate persistence of benefit at study endpoint, 24 weeks after randomization. During the 12-week treatment period, participants will undergo evaluation at baseline and at clinic visits on weeks 2, 6 and 12 after randomization to assess pain, proper treatment use and side effects. During the subsequent 12-week follow-up period, pain and safety will continue to be assessed monthly by phone calls. All patients will also be assessed daily using an electronic diary (eDiary) to record pain and mood. T1-MRI, resting state fMRI DTI-MRI, and ASL will be performed at baseline and at the end of 12 weeks for individuals completing MRI.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 244 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Triple
Primary Purpose: Treatment
Official Title: D-cycloserine for the Treatment of Chronic, Refractory Low Back Pain
Actual Study Start Date : March 30, 2018
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Back Pain
Drug Information available for: Cycloserine

Arm Intervention/treatment
Experimental: D-cycloserine
D-cycloserine 200 mg BID (twice daily)
Drug: D-cycloserine
200 mg BID (twice daily)

Placebo Comparator: Placebo
Placebo BID (twice daily)
Drug: Placebo
BID (twice daily)




Primary Outcome Measures :
  1. Change in Numeric Rating Scale (NRS) pain score [ Time Frame: 12 weeks ]
    Mean pain levels will be assessed at study baseline and compared to mean pain levels at Week 12 (study efficacy endpoint). Pain will be assessed using an 11-point NRS scale.


Secondary Outcome Measures :
  1. Gender (male/female) [ Time Frame: 12 weeks ]
    Assess the effect of gender on magnitude of pain response

  2. Brain biomarkers (MRI) [ Time Frame: 12 weeks ]
    Evaluate interaction between the primary endpoint and specified brain biomarkers, with particular attention to corticostriatal connectivity. Whole-brain exploratory analyses will also be used to identify both brain predictors or treatment response and brain reorganization in response to treatment.

  3. McGill Pain Questionnaire (MPQ) [ Time Frame: 12 weeks ]
    A 17-item self-reported measure assessing both the quality and intensity of subjective pain.

  4. painDETECT Questionnaire (PDQ) [ Time Frame: 12 weeks ]
    A 14-item self-reported measure assessing qualities for pain of neuropathic origin to distinguish pain severity.

  5. Beck Depression Inventory (BDI) [ Time Frame: 12 week ]
    A 21-item self-report rating inventory that measures characteristic attitudes and symptoms of depression.

  6. Positive and Negative Affect Schedule (PANAS) [ Time Frame: 12 weeks ]
    A self-report questionnaire consisting of two 10-item (5-point) scales to measure both positive and negative affects of pain.

  7. Pain Catastrophizing Scale (PCS) [ Time Frame: 12 weeks ]

    A 13-item scale assessing the degree of catastrophic cognitions in the sensation of pain.

    The scale ranges from 1 (not at all) to 4 (always).


  8. Multidimensional Assessment of Interoceptive Awareness (MAIA) [ Time Frame: 12 weeks ]
    A 32-item self-reported measure delineating between beneficial versus maladaptive interoceptive attention.

  9. Oswestry Disability Index (ODI) [ Time Frame: 12 weeks ]
    A 10-item self-reported measure quantifying a subjective percentage score of level of function (disability) in activities of daily living in those with chronic low back pain.

  10. SF-12 Health Survey [ Time Frame: 12 weeks ]
    A 12-item self-report questionnaire measuring functional health and well-being from the patient's point of view.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must have a history of low back pain for a minimum of 6 months with or without signs and symptoms of radiculopathy
  • Male or female, age 18 years or older, (no racial/ethnic restrictions)
  • Must have an average pain score of ≥ 4 (on a 0-10 NRS) over a 5 day period (total of at least 10 measures recorded in eDiary) immediately preceding the baseline visit (visit 2)
  • Must be willing to read and able to understand instructions as well as PROs
  • Must be in generally stable health
  • Must sign an informed consent document after complete explanation of the study documenting that they understand the purpose of the study, procedures to be undertaken, possible benefits, potential risks, and are willing to participate
  • Must be willing to discontinue all pain medications for chronic back pain (listed below) except the study medication and rescue medication provided and not use the following prohibited pain medications throughout the duration of the treatment period

    • analgesics including OTC medications
    • NSAIDS including OTC medications
    • Coxibs
    • Opioids
    • Muscle relaxants
    • Antidepressants for the treatment of low back pain
    • Antidepressants for therapeutic use (i.e. tricyclic antidepressants, SSRIs, SNRIs; low doses may be allowed)
    • Benzodiazepines
    • Sedatives/hypnotics
    • Anxiolytics
    • Gabapentinoids including pregabalin and gabapentin
  • Must be willing to comply with recording pain, mood, and study treatment adherence twice daily using study eDiary
  • Must be willing to abstain from drinking alcohol during the course of the study.
  • If female, must be post-menopausal for at least one year or practicing an accepted, highly effective method of contraception or abstinence and plan to continue during the course of the study.

Exclusion Criteria:

  • Low back pain associated with any systemic signs or symptoms, e.g., fever, chills.
  • Evidence of rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures, fibromyalgia, history of surgery or tumor in the back.
  • Involvement in litigation regarding their back pain or has a disability claim or is receiving workman's compensation or is seeking either as a result of their low back pain
  • History of seizures
  • Major psychiatric disorder during the past 6 months
  • Moderate or severe depression or any active suicidal ideation
  • Significant renal disease or severe renal insufficiency
  • History of, or current, substance abuse/dependence including alcohol
  • Significantly abnormal laboratory values
  • Pregnant or lactating at the time of randomization
  • Known sensitivity to D-cycloserine
  • Currently taking any of the following medications: ethionamide, dilantin, isoniazid (INH), pyridoxine (vitamin B6)
  • In the judgment of the investigator, unable or unwilling to follow the protocol and instructions
  • Any change in medication or physical therapy regime for back pain in the last 30 days.
  • Chronic progressive neurologic conditions, including Parkinson's disease, Alzheimer's disease, and other conditions associated with dementia
  • Significant other medical disease such as congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease, or malignancy
  • Presence of undiagnosed skin lesions or history of melanoma
  • Use of therapeutic doses of antidepressant medications (i.e., tricyclic antidepressants, SSRIs, SNRIs; low doses used only in the evening for sleep will be allowed if dose is not changed
  • Current use of recreational drugs or recent history of alcohol abuse or drug abuse
  • Current use of medical marijuana
  • High dose opioid prophylaxis, defined as > 50mg morphine equivalent/day
  • Intra-axial implants (e.g. spinal cord stimulators or pumps)
  • Pregnancy or inability to use an effective method of birth control in sexually active men and women while taking the study drug and for one week thereafter. Barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUD's), hormonal contraceptives, oral contraceptive pills, surgical sterilization, and complete abstinence are examples of effective methods of contraception.
  • Following laboratory abnormalities: liver function tests (SGOT/SGPT) greater than 2.5 times the upper limit of normal; unexplained anemia; evidence of renal insufficiency (creatinine > upper limit of normal) or any other abnormality that the principal investigator feels puts the participant at risk during the study.
  • Any medical condition that in the investigator's judgment may prevent the individual from completing the study or put the individual at undue risk
  • Lactose allergy
  • Ongoing participation in another clinical research study involving an investigational product or having received another investigational product within the last 90 days

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03535688


Contacts
Contact: Byron Yip, MSc 312-503-4856 b-yip@northwestern.edu

Locations
United States, Illinois
Northwestern University Feinberg School of Medicine Recruiting
Chicago, Illinois, United States, 60611
Contact: Thomas Schnitzer, MD, PhD    312-503-2315      
Sponsors and Collaborators
Northwestern University
United States Department of Defense
Investigators
Principal Investigator: Thomas J. Schnitzer, MD, PhD Northwestern University

Responsible Party: Thomas J. Schnitzer, Professor, Northwestern University
ClinicalTrials.gov Identifier: NCT03535688     History of Changes
Other Study ID Numbers: STU00205398
A-20364 ( Other Grant/Funding Number: Department of Defense )
First Posted: May 24, 2018    Key Record Dates
Last Update Posted: May 24, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Thomas J. Schnitzer, Northwestern University:
Chronic Pain
Low Back Pain
D-cycloserine

Additional relevant MeSH terms:
Back Pain
Low Back Pain
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Cycloserine
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action