Biomarkers for Prediction of Analgesic Efficacy Based on Interrelations Between Pain Modulation and EEG vs. Drugs' Mode of Action in Knee OA
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- CPM, a psychophysical parameter for pain inhibition, NPS
研究概览
简要总结
With high NNTs for indiscriminative use in chronic pain, treatment unavoidably entails frustrating long trial and errors. It is timely to identify biomarkers that can predict analgesic efficacy for the individual patient.
The investigators propose a framework of interrelations between patient's pain modulation profile (PMP) and the drug's mode of action (MOA) based on two principles: (1) 'fix the dysfunction', relevant for drugs whose main mode of action is to modulate central pain processing; the more the dysfunctional the better the modulating drug efficacy. For example, patients with pro-nociceptive PMP due to reduced endogenous pain inhibition, as expressed by less efficient CPM will benefit from drugs that fix this dysfunction such as SNRIs, relative to patients whose pain inhibitory capacity is well functioning. Thus, for the modulating drugs, pro-nociceptivity predicts better efficacy. (2) 'bear with the dysfunction', relevant for drugs which are mostly non-modulating, acting mainly in the periphery; the more dysfunctionalת the less the non-modulating drug efficacy. This is since efficacy is limited by the dysfunctional modulation system, despite the drug's MOA-like reduction of peripheral pain mediators. Thus, for the non-modulating drugs, for example NSAIDs, pro-nociceptivity predicts less good efficacy. The likely protocol suggests that patients with anti-nociceptive PMP should be treated primarily by non-modulating drugs, while pro-nociceptive ones should be given modulating drugs.
EEG is an additional source of relevant data on brain pain processing. Being objective and stable along time, EEG based parameters are, thus, very attractive candidates to be useful biomarkers for prediction of analgesia efficacy.
This study will focus on the patients with painful knee osteoarthritis.
The aims of this study are:
- To identify psychophysical and neurophysiological biomarkers that can serve as predictors of response to analgesic pain modulating and non-pain modulating drugs.
- To establish a conceptual framework of individualized pain therapy based on inter-relations between patient's parameters of pain modulation and drugs' mode of action.
详细描述
Study design:
The study design includes two experimental meeting sessions (before and at the end / after the treatment) which include clinical and experimental assessments. After the first experimental session, the patients will be asked to rate twice a week their daily pain along two weeks, in order to confirm their OA pain level; the patients with the mean pain score of ≥4 will be supplied with the study medications. Along the 8 weeks-long treatment period, they will provide the rating of OA pain, subjective estimation of pain alleviation and reports of side effects
Clinical assessment: Will be performed by the study physician. The data on OA severity by Kellgren and Lawrence system classification, range of motion and current OA pain (last 48 h) will be collected. In addition, all patients will fill the brief pain inventory questioner (BPI) to assess their pain characteristics. In addition, all patients will be tested for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for assessment of OA pain, stiffness and physical function.
Experimental session:
- At the beginning of pre-treatment experimental session, all patients will fill a following set of psychological pain-related questioners organized in one document: (1) pain catastrophizing scale (PCS), (2) HADS anxiety and depression, (3) short-form health survey (SF-12), (5) pain sensitivity questionnaire (PSQ). In addition, basic assessment of psychomotor attention and cognitive functioning will be performed using (6) Trial making tests A and B (TMT A and B) and (7) Digits symbol substitution test (DSST). All the data will be coded and no personal data will be exposed.
- Resting-state EEG recording. Three minutes of resting-state EEG (eyes closed) will be recorded using the 64-channel EEG recording (Brain Products GmbH, Munich, Germany).
- Psychophysical pain assessment. All tests will be performed remotely from the painful area - on arm or hand. The following tests will be performed:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •males and females
- •ages 45 to 75
- •radiographic representation of osteoarthritis of the knee
- •minimal or moderate OA severity, based on the Kellgren and Lawrence system classification (1-3)
- •knee OA pain for more than 3 months, assessed by the patients as being at level 4/10 and above on average at routine daily standing/walking activities during the last week, without medication
排除标准
- •other more prominent pain
- •previous bilateral total knee replacement (TKR) surgery
- •secondary OA (post-traumatic or post-infectious, osteochondritis dissecans (OCD) and enteropathic arthritis (EA) deformity)
- •significant additional health problems such as substantial painful neuropathy, diabetes above of 5 yrs, renal failure, congestive heart failure, neurological diseases that might mask the pain processing system or reduce patient's cooperation or report capabilities, and significant psychiatric disorders
- •use of opioids or cannabis
- •known diseases of gastrointestinal tract such as esophagitis, gastritis and duodenitis
- •patients that had side effects to the study drugs in the past.
研究组 & 干预措施
Duloxetine
Eight weeks treatment, one pill a day. Week 1st - 30 mg a day. Weeks 2nd - 8th - 60 mg a day.
干预措施: Duloxetine 60mg (Drug)
Etoricoxib
Eight weeks treatment. 60 mg daily pill ; from the second week adding omeprazol 20 mg daily
干预措施: Etoricoxib 60 mg (Drug)
Etoricoxib
Eight weeks treatment. 60 mg daily pill ; from the second week adding omeprazol 20 mg daily
干预措施: omeprazol (Drug)
结局指标
主要结局
CPM, a psychophysical parameter for pain inhibition, NPS
时间窗: up to 2 years
Post vs pre-treatment changes in Conditioned Pain Modulation (CPM)
TS, a psychophysical parameter for pain facilitation, NPS
时间窗: up to 2 years
Post vs pre-treatment changes in Temporal Summation of pain (TS)
resting-state EEG theta power, microvolts
时间窗: up to 2 years
Post vs pre-treatment changes in the EEG power within theta band
resting-state EEG alpha power, microvolts
时间窗: up to 2 years
Post vs pre-treatment changes in the EEG power within alpha band
Clincial pain, VAS
时间窗: up to 2 years
Post vs pre-treatment changes in VAS
Pain-related disability, numerical scores
时间窗: up to 2 years
Post vs pre-treatment changes (disability score)
次要结局
未报告次要终点