D-cycloserine in the Management of Chronic Low Back Pain

Phase 2

Completed

Conditions: Low Back Pain
Pain

Interventions: Drug: placebo
Drug: D-cycloserine

Registration Number: NCT00125528

Lead Sponsor: Thomas J. Schnitzer

Brief Summary: Pre-clinical studies in rats suggest that D-cycloserine (DCS) 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 chronic low back pain. Other aims of this study are to determine the safety of D-cycloserine in the treatment of chronic low back pain and to determine which pain measurement scales are best at measuring the efficacy of treatment.

Detailed Description: 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, the investigators 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 the investigators hypothesize that chronic neuropathic pain (back pain with radiculopathy) is partially mediated or potentiated by decreased ability to extinguish the pain memory, which the investigators hypothesize to be mediated through reward/aversion brain circuitry, and specifically through medial prefrontal cortex. They 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, the investigators 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 escalating dose study comparing D-cycloserine twice a day (bid) with placebo bid in patients with chronic low back pain. Subjects meeting inclusion criteria will continue baseline medications and be treated for 12 weeks with study drug: 50 mg bid DCS or matching placebo for the first 4 weeks, then 100mg bid DCS or matching placebo for 4 weeks and finally 200mg bid DCS or matching placebo for 4 weeks. 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 41

Inclusion Criteria

Must have a history of low back pain for a minimum of 6 months with or without radiation of pain to leg or buttocks.
Must be 18 years of age.
Must have a visual analogue scale (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 have a disability claim or are 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	placebo	placebo
1	D-cycloserine	D-cycloserine 50mg bid/100mg bid/200 mg bid

Primary Outcome Measures

Name	Time	Method
Change in Numeric Rating Scale (NRS-11)	6 weeks	Change in NRS score after 6 weeks of treatment as compared to baseline. The numeric rating scale is an 11-point rating scale wherein participants rated their current lower back pain intensity on a scale from 0 to 10, with 0 meaning no pain and 10 being the worst pain possible. Thus, a larger negative number indicates positive change and a higher efficacy.

Secondary Outcome Measures

Name	Time	Method
McGill Pain Questionnaire (MPQ)	6 weeks	Change in MPQ score after 6 weeks of treatment as compared to baseline. The MPQ score uses a Pain Rating Index from 0 to 20 where 0 is evidence of no pain and 20 indicates the highest pain possible. A lower score is also indicative of a lower quality of pain. Thus, a larger negative number indicates positive change and therefore higher efficacy.