Pre-clinical studies in rats suggest that D-cycloserine is effective in the management of chronic neuropathic pain. This pilot study will attempt to determine the effect of D-cycloserine in the treatment of neuropathic chronic low back pain. Other aims of this study are to determine the safety of D-cycloserine in the treatment of neuropathic chronic low back pain and to determine which pain measurement scales are best at measuring the efficacy of treatment.

Condition	Intervention	Phase
Low Back Pain Pain	Drug: D-cycloserine	Phase II

Further Study Details: 

Primary Outcomes: Determine efficacy of D-cycloserine in the treatment of chronic low back pain.
Secondary Outcomes: Determine safety profile of D-cycloserine in the treatment of neuropathic chronic low back pain.; Evaluate response characteristics of various outcome measures to D-cycloserine treatment in these subjects.
Expected Total Enrollment:  39

Human brain imaging studies indicate that the medial prefrontal cortex activity can predict more than 80% of the variance of chronic back pain intensity. Therefore, we have hypothesized that modulation of brain activity at this site should result in analgesia. D-cycloserine has been shown to potentiate conditioned fear extinction. Based on this we hypothesize that chronic neuropathic pain (back pain with radiculopathy) is partially mediated or potentiated by decreased ability to extinguish the pain memory, which we hypothesize to be mediated through reward/aversion brain circuitry, and specifically through medial prefrontal cortex. We have tested this idea in pre-clinical studies and demonstrated that rats with neuropathic pain show analgesia over the long-term when treated with D-cycloserine. In humans with chronic back pain, we hypothesize that D-cycloserine will enhance extinction of back pain which in turn should result in reduced emotional relevance of the pain, that is reduced suffering. It is quite possible that the overall intensity of the back pain will be unaffected, however, the associated suffering will be significantly attenuated.

This will be a double-blind, randomized, parallel group study comparing D-cycloserine at 250mg bid with placebo in patients with neuropathic chronic low back pain. Subjects meeting inclusion criteria will continue baseline medications and be treated for 4 weeks with study drug, followed by a 2 week blinded placebo treatment period and a subsequent 4 weeks of treatment with the same study drug as the initial treatment period. Assessments of efficacy and safety will be undertaken every 2 weeks using standard, validated instruments to evaluate change in pain, function, quality of life and adverse events.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Must have a history of low back pain for a minimum of 6 months with radiation of pain to leg or buttocks.
• Must be 18 years of age.
• Must have a VAS pain score >50 mm
• Must be in generally stable health
• 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 either during the course of the study.
• Must be able and willing to read and understand instructions as well as questionnaires
• 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.

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 seeking either as a result of their low back pain
• Neurologic disorder, including history of seizures
• Major psychiatric disorder during the past 6 months
• Moderate or severe depression as determined by the Beck Depression Inventory or any active suicidal ideation
• Significant other medical disease such as unstable diabetes mellitus, congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease, or malignancy
• Significant renal disease or severe renal insufficiency
• History of, or current, substance abuse/dependence including alcohol
• Significantly abnormal laboratory values
• Pregnant or lactating at any time during the course of the study
• 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 for back pain in the last 30 days.

Please refer to this study by ClinicalTrials.gov identifier  NCT00125528

Thomas J Schnitzer, MD, PhD      312-503-1500    tjs@northwestern.edu

Illinois
      Northwestern Center for Clinical Research, Northwestern University, Chicago,  Illinois,  60611,  United States
      Rehabiliation Institute of Chicago, Chicago,  Illinois,  60611,  United States

Study chairs or principal investigators

Thomas J Schnitzer, M.D., Ph.D.,  Principal Investigator,  Northwestern University   
Vania Apkarian, Ph.D.,  Principal Investigator,  Northwestern University   
Norman Harden, M.D.,  Principal Investigator,  Rehabilitation Institute of Chicago   

Study ID Numbers:  A1159
Last Updated:  August 1, 2005
Record first received:  July 29, 2005
ClinicalTrials.gov Identifier:  NCT00125528
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-08-02