Clinical trial NCT00125528: D-cycloserine in the Management of Chronic Low Back Pain
Official title: D-Cycloserine in the Management of Chronic Low Back Pain: A Double-Blind, Randomized, Placebo-Controlled Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Low Back Pain
Pain
Keywords: chronic pain
low back pain
D-cycloserine
Lead sponsor: Northwestern University
Sponsor class: OTHER
First posted: 2005-08-01
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Numeric Rating Scale (NRS-11)
timeFrame: 6 weeks
Secondary outcomes:
measure: McGill Pain Questionnaire (MPQ)
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
Study officials:
affiliation: Northwestern University
name: Thomas J Schnitzer, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University
name: Vania Apkarian, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schnitzer TJ, Torbey S, Herrmann K, Kaushal G, Yeasted R, Vania Apkarian A. A randomized placebo-controlled pilot study of the efficacy and safety of D-cycloserine in people with chronic back pain. Mol Pain. 2016 Nov 15;12:1744806916678627. doi: 10.1177/1744806916678627. Print 2016.