D-cycloserine for the Treatment of Chronic, Refractory Low Back Pain
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 203
- 试验地点
- 2
- 主要终点
- Change in Numeric Rating Scale (NRS) pain score 0-10; higher worse
研究概览
简要总结
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.
详细描述
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. Magnetic resonance imaging (MRI), anatomical MRI, resting state functional MRI (fMRI), diffusion-tensor imaging (DTI) MRI, and arterial spin labeling (ASL) will be performed at baseline and at the end of 12 weeks for individuals completing MRI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Triple
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 5-7 day period (minimum of daily eDiary entries for at least 5 of 7 days) immediately preceding the baseline visit (visit 2)
- •Must be willing to read and able to understand instructions as well as patient reported outcomes (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 over the counter (OTC) medications
- •NSAIDS including OTC medications
- •Muscle relaxants
- •Gabapentins 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.
排除标准
- •Low back pain associated with any systemic signs or symptoms, e.g., fever, chills
- •Evidence of rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures, fibromyalgia, or history of surgery or tumor in the back within the past 6 months
- •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
- •Epidural steroid injection within the past 3 months
- •History of seizures
- •Major new or untreated psychiatric disorder during the past 6 months and/or ongoing treatment with buproprion or fluphenazine
- •Beck Depression Inventory II score of >28
- •Significant renal disease or severe renal insufficiency
- •Substance abuse/dependence including alcohol within the past 6 months
- •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)
- •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
- •Other medical disease such as clinically significant congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease, or malignancy
- •Presence of undiagnosed skin lesions or history of melanoma
- •Current use of recreational drugs
- •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
研究组 & 干预措施
Placebo
Placebo twice daily
干预措施: Placebo (Drug)
D-cycloserine
D-cycloserine 200 mg twice daily
干预措施: D-cycloserine (Drug)
结局指标
主要结局
Change in Numeric Rating Scale (NRS) pain score 0-10; higher worse
时间窗: 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.
Change in Numeric Rating Scale (NRS) Pain Score 0-10; Higher Worse
时间窗: 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.
次要结局
- Beck Depression Inventory (BDI)(12 week)
- Positive and Negative Affect Schedule (PANAS)(12 weeks)
- Multidimensional Assessment of Interoceptive Awareness (MAIA)(12 weeks)
- Gender (male/female)(12 weeks)
- Brain biomarkers (MRI)(12 weeks)
- PainDETECT Questionnaire (PDQ)(12 weeks)
- McGill Pain Questionnaire (MPQ)(12 weeks)
- Pain Catastrophizing Scale (PCS)(12 weeks)
- Oswestry Disability Index (ODI)(12 weeks)
- 12-Item Short Form Survey (SF-12)(12 weeks)
- Effect of Gender on Magnitude of Pain Response.(12 weeks)
- Brain Biomarkers (MRI)(12 weeks)
- Positive and Negative Affect Schedule (PANAS) - Positive(12 weeks)
- 12-Item Short Form Survey (SF-12) - Mental(12 weeks)
- Positive and Negative Affect Schedule (PANAS) - Negative(12 weeks)
- 12-Item Short Form Survey (SF-12) - Physical(12 weeks)
- Patient Global Assessment(12 weeks)
- Patient Global Impression of Change(12 weeks)
研究者
Thomas J. Schnitzer
Professor
Northwestern University