Ultra-early Gamma Knife Stereotactic Radiosurgery for Trigeminal Neuralgia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Primary outcome measure--pain
研究概览
简要总结
The goal of this clinical trial is to evaluate Gamma Knife stereotactic radiosurgery (GK-SRS) as an ultra-early treatment option for trigeminal neuralgia (TN).
The main questions it aims to answer are:
- will earlier GK-SRS provide more durable pain relief compared to later GK-SRS?
- will earlier GK-SRS reduce or eliminate the need for high-dose medical therapy?
- will earlier GK-SRS have a lower risk of serious complications compared to other first-line treatments?
If participants are assigned to GK-SRS treatment group, they will be asked to:
• Undergo a preoperative MRI, measurements of heart rate and blood pressure, stereotactic head-frame placement, post-operative management and observation.
Both groups will be asked to:
- Complete medical histories and neurological examinations. These are part of standard of care.
- Participants will be asked a series of questions related to overall physical health, pain severity, and mood. Completing these questionnaires is part of the research activity. It will take approximately 15- 30 minutes to complete. These questionnaires include: The Barrow Neurological Institute Pain Intensity Score, Brief Pain Inventory-Facial (BPI-Facial), Visual Analog Scale (VAS), Medication Quantification Scale (MQS), Hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale (PCS), and the Short Form Health Survey.
详细描述
Background Trigeminal neuralgia (TN) is a chronic, often debilitating, neuropathic facial pain condition with an approximate global incidence of 12 cases per 100,000 and a female predominance of 3:2, occurring predominantly in the sixth decade of life and increases with age, peaking around 70 years. According to the International Classification of Headache Disorders (ICHD-3), TN is characterized by "recurrent unilateral brief electric shock-like pains, abrupt in onset and termination, limited to the distribution of one or more divisions of the trigeminal nerve (cranial nerve five - CNV) and triggered by innocuous stimuli". The CNV divides into three distinct subdivisions that carry sensory information from the scalp, forehead, eyes, upper and lower eyelids, mucous membranes of the nasal and oral cavities, frontal sinus, cheeks, teeth, lower and upper lips, and deep structures within the head. The severe lancinating pain of TN may be triggered by common somatosensory stimuli experienced in everyday life, such as chewing, speaking, brushing teeth, temperature changes, or tactile pressure to the face; pain attacks may also occur entirely spontaneously.
Given the severity of this condition, prompt pain management is critically important. Generally, pharmaceutical therapy is employed as the first-line treatment, usually in the form of antiepileptic drugs which are known to be effective against neuropathic pain, with carbamazepine (CBZ) being the gold standard. Unfortunately, these agents pose a significant risk of adverse effects ranging from ataxia, double vision, hyponatremia, confusion, and tremor, to more severe complications such as cardiac arrhythmia, aplastic anemia, hepatotoxicity, toxic epidermal necrolysis, and dosages reaching toxic levels. Frequently, increased doses are required to maintain therapeutic pain relief over time. Indeed, while pharmaceuticals may be the standard first-line treatment for TN, >50% of patients eventually fail medical therapy. The combination of unfavourable adverse effects and diminished drug response can lead to prolonged disruption of overall well-being in a considerable proportion of patients with TN.
In general, surgical options (i.e., microvascular decompression (MVD), percutaneous rhizotomy (PR), and Gamma Knife stereotactic radiosurgery (GK-SRS)) are reserved for patients who are classified as "medically refractory". In essence, surgical treatment is offered as a rescue therapy when pharmaceutical management has failed. Of the surgical options, GK-SRS is a highly precise type of radiation therapy which is by far the least invasive, carrying with it the lowest risk of serious adverse surgery-related risks. There is good evidence to support the safety and efficacy of GK-SRS in medically-refractory TN, with some data suggesting that earlier intervention (within 3-4 years of pain onset) may result in better long-term pain outcomes. However, what is not known is whether ultra-early intervention with GK-SRS-before the actual development of medical-refractoriness-could somehow alter the natural progression of TN, thereby avoiding the need for high-dose medical therapy altogether and the side effects associated with it.
Objective
The investigators aim to evaluate the feasibility and potential benefit of GK-SRS as an ultra-early treatment option for TN. Given the well-established tolerability of GK-SRS, it is hypothesized that ultra-early GK-SRS will:
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
- None
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
- •Age ≥18 years
- •Clinical diagnosis of classical or idiopathic TN, based on clinical history and MRI scan
- •Clinical diagnosis within 2 years prior to enrolment
- •Not deemed medically refractory (defined as adequate pain control despite ≥2 medication trials of adequate dose. Adequate pain control is defined as pain that is considered acceptably controlled by both the patient and treating neurologist, without the need for further dose escalation)
- •If currently on medication, on stable dose x at least 3 months
排除标准
- •Secondary TN
- •Bilateral TN
- •Any contraindications to undergoing GK-SRS
- •Any prior cranial radiation
- •Any prior surgical intervention for TN
- •History of psychiatric diagnoses within 2 years of study participation, or uncontrolled, concurrent psychiatric illness (e.g., depression with recent suicide attempts)
- •Females who are pregnant or breast-feeding
研究组 & 干预措施
Standard arm
Patients allocated to the standard arm will continue their medical management per the judgment of treating physician.
Gamma Knife stereotactic radiosurgery for TN
干预措施: GK SRS (Procedure)
结局指标
主要结局
Primary outcome measure--pain
时间窗: 2 years after the day of GK-SRS treatment, for participants in the Experimental Arm. 2 years after enrolment, for participants in the No-intervention Arm.
The primary endpoint is satisfactory pain control at 2 years after GK-SRS treatment (for Experimental Arm) or 2 years after enrolment in the Non-intervention Arm, measured using Barrow Neurological Institute Facial Pain Scale (BNI). Satisfactory pain control = BNI I, II, IIIa Barrow Neurological Institute Facial Pain Scale (BNI) I - no pain, no medication II - occasional pain, no medication required III - some pain, adequately controlled with medication IIIa - no pain, continued medication IIIb - persistent pain, controlled with medication IV - some pain, not adequately controlled with medications V - severe pain or no pain relief (lower scores indicate better outcome)
次要结局
- Secondary outcome measure - treatment-related adverse events(At 6, 12, 24 months, and 5 years after the day of GK-SRS treatment, for participants in the Experimental Arm. At 6, 12, 24 months, and 5 years after enrolment, for participants in the No-intervention Arm)
- Secondary outcome measure - medication(Experimental Arm: Baseline visit; GK-SRS treatment visit; follow-up visits 6, 12, 24 months, and 5 years after day of GK-SRS treatment. No-intervention Arm: Baseline visit; follow-up visits 6, 12, 24 months, and 5 years after enrolment)
- Secondary outcome measure - complete pain relief(2 years after the day of GK-SRS treatment)
- Secondary Outcome Measure - long term satisfactory pain relief(5 years after day of GK-SRS treatment)
- Secondary Outcome Measure - facial numbness(At 6, 12, 24 months, and 5 years after GK-SRS treatment)
- Secondary outcome measure - crossover(At 6, 12, 24 months, and 5 years after enrolment)
- Secondary outcome measure - repeat surgical referral(At 6, 12, 24 months, and 5 years after GK-SRS treatment)