Low Back Pain, Pain
Conditions
Keywords
chronic pain, low back pain, D-cycloserine
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.
Interventions
DRUGD-cycloserine
D-cycloserine 50 mg bid; D-cycloserine 100 mg bid; D-cycloserine 200 mg bid
DRUGplacebo
placebo bid
Sponsors
Thomas J. Schnitzer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| D-cycloserine D-cycloserine: D-cycloserine 50 mg bid; D-cycloserine 100 mg bid; D-cycloserine 200 mg bid | 20 |
| Placebo placebo: placebo bid | 21 |
| Total | 41 |
Baseline characteristics
| Characteristic | D-cycloserine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 54.65 years STANDARD_DEVIATION 11.56 | 54.76 years STANDARD_DEVIATION 10.84 | 54.71 years STANDARD_DEVIATION 11.06 |
| Gender Female | 14 Participants | 11 Participants | 25 Participants |
| Gender Male | 6 Participants | 10 Participants | 16 Participants |
| Numeric Rating Scale (NRS-11) | 6.47 units on a scale STANDARD_DEVIATION 1.4 | 6.6 units on a scale STANDARD_DEVIATION 1.5 | 6.54 units on a scale STANDARD_DEVIATION 1.45 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 20 | 5 / 21 |
| serious Total, serious adverse events | 0 / 20 | 0 / 21 |
Outcome results
Primary
Change in Numeric Rating Scale (NRS-11)
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.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-cycloserine | Change in Numeric Rating Scale (NRS-11) | -2.47 units on a scale | Standard Deviation 0.5 |
| Placebo | Change in Numeric Rating Scale (NRS-11) | -1.55 units on a scale | Standard Deviation 0.5 |
Secondary
McGill Pain Questionnaire (MPQ)
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.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-cycloserine | McGill Pain Questionnaire (MPQ) | -2.80 units on a scale | Standard Deviation 0.66 |
| Placebo | McGill Pain Questionnaire (MPQ) | -1.00 units on a scale | Standard Deviation 0.66 |