True Functional Restoration and Analgesia in Non-Radicular Low Back Pain: a Prospective, Double Blind, Placebo-controlled Study of Buccal Buprenorphine
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Patient global impression of function
研究概览
简要总结
To study the response of objective and quasi-objective 'True' functional outcomes, analgesia and safety in chronic non-radicular back pain to buprenorphine buccal film (BBF) using a small 'n' phase IV design. To assess associations between traditional pain relevant subjective outcomes and objective or quasi-objective functional outcomes; In a small 'n' construct, to assess more powerful, 'new' statistical methods (e.g. hierarchical linear models, joint trajectory analysis) compared to traditional methods, in the context of increased power, more objective outcomes and cost savings.
First a 2-week washout of any opioid medication (if necessary; if not necessary subject can proceed directly to); baseline week (Single Blind Placebo Lead In (SBPLI), using the placebo film resembling the 150mcg dose; then randomization to a ~ 2 week up titration either to effective Buprenorphine Buccal Film (BBF) dose 2 day average pain better than or equal to 3/10 NRS), highest tolerated dose BBF and/or maximum dose BBF of 900 mcg BID, or identical placebo material up to these parameters. This up titration is at the discretion and timing of the blinded and experienced PI. Subject will be allowed two doses of hydrocodone/acetaminophen 5/325 daily during the washout period.
A single experienced practitioner will manage the titration as to safety, detail and timing; and determine when the subject enters the 8 week stable dose trial; this practitioner will remain blinded throughout unless there is an urgent, safety reason for unblinding
详细描述
Scientific/Medical Rationale:
Improved function is a high yield goal in back pain in specific, and pain in general. There are a number of self-report scales measuring 'physical functioning', 'quality of life' or ability to complete activities of daily living available. Unfortunately these tests, though sometimes mentioned as 'tests of physical function', retain the significant limitation of being fully subjective as they rely entirely on subject perception and report. These subjective metrics are considered useful in that they show good preliminary correlation with measured functional abilities and true functional performance. There have been many attempts to bring more objective and quantitative functional scales to bear, and these efforts have achieved variable success. Scales that are recorded by a professional observer, such as a physical therapist, lend more 'objectivity' to the assessment, as with the Barthel index. The Functional Capacities Evaluation (FCE) type metrics are highly validated, although geared more toward patients with back pain in the forensic arena. As such they are not as yet practical in the context of CLBP research, multi-center trials, or even the clinic.
Subjective, yet quantified pain ratings are commonly used to follow a patient's response to analgesic treatment,and although having good clinical value for within-subject comparison, between-subject contrasts are less reliable. Multiple factors including culture, memory, the meaning and context of pain, personality types, affective state and a variety of operant variables can influence reported pain,making these outcomes less scientifically adequate than more objective outcomes.
Objective and Quasi-objective instruments have been developed to assess some relevant aspects of the pain experience. For instance, gross functional assessments, such as return to work and health care utilization, have been adapted and validated for pain research. While fully objective testing such as fMRI holds the promise of being able to quantify human pain, this will not be practical in the near future. As there will always be a need for simple "bedside" measures and practical pain laboratory testing, as well as a great need to add objectivity to this otherwise subjective diagnostic set. Logically, function should be a high priority outcome in pain research.
Many measures have been validated over the years that can concurrently assess psychological spheres of the pain experience. While it is clear that the impact of pain and mood are critical components for characterizing the overall clinical pain experience, unfortunately the pain literature is based entirely on self-report psychometric scales, and the subjective nature of these measures make them less than fully satisfactory for research. Thus, there is a critical need to shift the paradigm away from subjective measures (where possible) to more objective methodologies. It is likely that objectification will lower cost in clinical trials through the mechanism of improved power (thus lower numbers of subjects required to demonstrate statistical response).
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, Care Provider, Investigator)
盲法说明
Two designated staff will be unblinded, and be responsible for providing the subjects with envelopes containing either drug or placebo. Principal investigator and the remainder of the staff will be blinded throughout the duration of the study.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Meets our criteria for CNRBP:
- •Pain of 3 months or more duration
- •non-radiating (below buttocks or above lower back pain)
- •no decreased sensation or allodynia/hyperalgesia in a radicular pattern
- •no reflex asymmetry
- •no frank weakness or atrophy
- •no non-pain sensory or reflex changes
- •If female, not pregnant or breast feeding, and not currently attempting to conceive; if of childbearing potential, use of a highly effective method of birth control (as determined by Pl).
- •Able to read and speak English and provide informed consent.
- •Able to understand and comply with all data collection methodology, and demonstrated ability to manage the electronic diary system (as tested in 'detox' and baseline/SBPLI period).
- •Subjects may continue any non-opioid stable scheduled drug regimen with no changes during the course of study, hydrocodone/acetaminophen 5/325 up to two doses per day along with Tylenol 2g/day are the only allowed rescue medications. Subjects are asked not to use the rescue medication 12 hours or less before testing.
- •Subjects taking opioids must agree to 'detoxify' for the protocol under the supervision of the study medical personnel. Subjects may use hydrocodone/acetaminophen 5/325 twice daily for breakthrough pain, as provided to them during the study, and must use only the hydrocodone/acetaminophen provided (with a pill count is a secondary outcome)
- •Subjects must agree to try to stay as functional as possible (defined by only tolerable increase in pain with function or function testing)
- •Must have 'average' pain greater than or equal to 4 and no greater that 9 on a 10-point NRS scale at phone screening and first visit
- •Subjects must have and maintain a working phone
- •CMP, CBC, UDS, EKG within normal limits at the discretion of the PI.
排除标准
- •Subjects with hypersensitivity to Opioids, Acetaminophen, buprenorphine or Belbuca®
- •Subjects taking equal to or more than 100 morphine milliequivalents,
- •Subjects with severe or untreated psychiatric disturbance (e.g. mania, depression [esp suicidality], anxiety, substance use disorder etc). This exclusion at the discretion of the PI.
- •A known or admitted history of opioid abuse, diversion or addiction.
- •Subjects with severe, ongoing or unaddressed medical conditions (e.g. Renal or Hepatic disease i. [creatinine>1.5 ml/dl; AST or ALT> 2x normal limit], severe or uncontrolled hypertension, pulmonary ii. disease, seizure disorder or gastroparesis or urinary retention.
- •Subjects with a clinical diagnosis of fibromyalgia, polymyalgia rheumatica, spinal stenosis or non-osteoarthritis i. rheumatologic disease or severe chronic pain disorder of other body regions.
- •Subjects who are currently talking MAO inhibitors (must have been off for > 14 days)
- •Subjects with planned surgery or invasive/interventional procedures.
- •Subjects must be willing to comply with visit and phone contact schedule, and try to stay as active and 'functional' as they can.
- •Subjects cannot be involved in any litigation concerning Workers Compensation or lawsuit concerning injury.
研究组 & 干预措施
Active drug arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided placebo buprenorphine buccal film that mimics the actual drug comparator and is continued by a blinded individual throughout the duration of the trial.
干预措施: Buprenorphine Buccal Film [Belbuca] (Drug)
Active drug arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided placebo buprenorphine buccal film that mimics the actual drug comparator and is continued by a blinded individual throughout the duration of the trial.
干预措施: Urine Drug Screening (Other)
Active drug arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided placebo buprenorphine buccal film that mimics the actual drug comparator and is continued by a blinded individual throughout the duration of the trial.
干预措施: actigraph (Device)
Active drug arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided placebo buprenorphine buccal film that mimics the actual drug comparator and is continued by a blinded individual throughout the duration of the trial.
干预措施: PROMIS 29 (Behavioral)
Active drug arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided placebo buprenorphine buccal film that mimics the actual drug comparator and is continued by a blinded individual throughout the duration of the trial.
干预措施: sit to stand test (Other)
Active drug arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided placebo buprenorphine buccal film that mimics the actual drug comparator and is continued by a blinded individual throughout the duration of the trial.
干预措施: numerical rating scale pain score (Other)
Active drug arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided placebo buprenorphine buccal film that mimics the actual drug comparator and is continued by a blinded individual throughout the duration of the trial.
干预措施: patient global impression of function (Behavioral)
Active drug arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided placebo buprenorphine buccal film that mimics the actual drug comparator and is continued by a blinded individual throughout the duration of the trial.
干预措施: PROMIS - sleep (Behavioral)
Placebo arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided active buprenorphine buccal film that is titrated to the effective dose and continued by a blinded individual throughout the duration of the trial.
干预措施: Urine Drug Screening (Other)
Placebo arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided active buprenorphine buccal film that is titrated to the effective dose and continued by a blinded individual throughout the duration of the trial.
干预措施: actigraph (Device)
Placebo arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided active buprenorphine buccal film that is titrated to the effective dose and continued by a blinded individual throughout the duration of the trial.
干预措施: PROMIS 29 (Behavioral)
Placebo arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided active buprenorphine buccal film that is titrated to the effective dose and continued by a blinded individual throughout the duration of the trial.
干预措施: sit to stand test (Other)
Placebo arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided active buprenorphine buccal film that is titrated to the effective dose and continued by a blinded individual throughout the duration of the trial.
干预措施: numerical rating scale pain score (Other)
Placebo arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided active buprenorphine buccal film that is titrated to the effective dose and continued by a blinded individual throughout the duration of the trial.
干预措施: patient global impression of function (Behavioral)
Placebo arm
Subjects who meet eligibility criteria and complete a single blind placebo lead in will be provided active buprenorphine buccal film that is titrated to the effective dose and continued by a blinded individual throughout the duration of the trial.
干预措施: PROMIS - sleep (Behavioral)
结局指标
主要结局
Patient global impression of function
时间窗: 20 weeks
2 questions administered through an e-dairy on a daily basis to assess subject's impression fo function. Numeric scale: 0 no functional impairment due to pain; 10 total functional impairment due to pain
activity -sleep
时间窗: 20 weeks
actigraph data, utilizing a garmin device, will be gathered recording time the subject was sleeping based on movements and heart rate in a 24 hour period
Patient Reported Outcomes Information System - 29
时间窗: 20 weeks
29 questions about mood, sleep, and function will be gathered on a weekly basis via e-diary. This is scored, with 29 being the best outcome, and 100 the worst
Sit to stand test
时间窗: 20 weeks
Function - subjects will perform sit to stand test to measure pain and ability to perform such activity to compare the placebo and active comparator groups.
Numberic Rating Scale
时间窗: 20 weeks
Numeric rating scale pain scores (0-10; 0- no pain, 10 - worst pain imaginable) will be recorded on a daily basis in the placebo and active comparator groups.
Patient Reported Outcomes Information System - Sleep
时间窗: 20 weeks
Subjects will be provided a 5 point scale to rate sleep which will be scored. 4 - 20 higher score shows the most sleep disturbance, lower score is no sleep disturbance
Activity - steps per day
时间窗: 20 weeks
Actigraph data, using a garmin device, will be gathered to record the number of steps the subject took in a 24 hour time period
Activity - time sitting
时间窗: 20 weeks
Actigraph data, using a garmin device. Time sitting in hours and minutes will be recorded on a 24 hour time block
Timed stair climb
时间窗: 20 weeks
9 steps will be ascended with or without the use of a handrail. Time will be recorded in seconds.
次要结局
- Sleep(20 weeks)
- Activity(20 weeks)
- Function(20 weeks)
- Bayesian analysis(20 weeks)