A Multidisciplinary Translational Approach to Investigate the Mechanisms, Predictors, and Prevention of Persistent Post-Traumatic Headache
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 6
- 试验地点
- 3
- 主要终点
- Change in the Number of Days Experiencing Moderate-to-Severe Headaches
研究概览
简要总结
This is a United States Department of Defense funded Focused Program study that aims to identify mechanisms and predictors for persistent of post-traumatic headache attributed to mild traumatic brain injury, and identify methods of preventing post-traumatic headache persistence.
The objective of the clinical trial component of the Focused Program is to determine whether intervention with erenumab is an effective treatment for PTH attributed to mTBI.
详细描述
The human studies component of this Focused Program includes clinical phenotyping, neurophysiology, molecular and genetic biomarker discovery, brain imaging, and a clinical trial.These data will be utilized to characterize post-traumatic headache and build univariate and multivariate predictive models for post-traumatic headache persistence and for the response to post-traumatic headache treatment. These studies are described in more detail within a separate clinicaltrials.gov record.
The clinical trial is a double-blind, randomized, placebo-controlled investigation of erenumab for the treatment of post-traumatic headache. Participants will be randomized when PTH has been present for 35-56 days. Follow-up questionnaires, headache diary data, pain threshold results, and brain imaging data will be collected longitudinally during the clinical trial to assess for changes over time and associations of such changes with post-traumatic headache treatment outcomes. Due to slow enrollment, the study was later changed to open label since the estimated total enrollment would be inadequate for making comparisons between the placebo and erenumab groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a diagnosis of acute PTH attributed to mild traumatic injury to the head as defined by the International Classification of Headache Disorders (ICHD-3).
- •PTH onset 7-56 days prior to the time of enrollment
- •Adults 18-70 years of age
- •Willing to be randomized to either of the two clinical trial treatment arms
- •Willing to maintain a headache diary
- •Willing and able to return for follow-up visits
- •4 or more moderate or severe headache days during the 4-week run-in phase and an increase of at least 2 moderate to severe headache days compared to pre-TBI and at least a 30% increase
- •At least 80% compliant with diary keeping during the 4-week run-in phase (i.e., provides data on at least 80% of days)
排除标准
- •Chronic headache (i.e., at least 15 headache days/month for more than 3 months) within 12 months prior to the mTBI that led to the current PTH, including PPTH, chronic migraine, medication overuse headache, new daily persistent headache, hemicrania continua, chronic tension-type headache
- •Diminished decision-making capacity that in the investigator's opinion would interfere with the person's ability to provide informed consent and complete study procedures
- •Started or changed dose of a headache preventive medication within the 3 months prior to screening
- •Use of onabotulinumtoxinA in the head, neck or face region within 6 months of screening
- •During the 6 months before screening, use of opioids or barbiturates on an average of at least 4 days per month
- •Subjects who underwent an intervention or used a device (e.g., nerve blocks, transcranial magnetic stimulation, vagal nerve stimulation, or electrical trigeminal nerve stimulation) for headache within 3 months of screening
- •History of major psychiatric disorder such as schizophrenia and bipolar disorder
- •History or evidence of any unstable or clinically significant medical condition, that in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
- •History of positive neuroimaging findings that indicate a moderate or severe TBI
- •Contraindications to magnetic resonance imaging, including, but not limited to (only an exclusion for patients participating in the brain MRI portion of this research):
- •Metal implants
- •Aneurysm clips
- •Severe claustrophobia
- •Implanted electronic device
- •Insulin or infusion pump
- •Cochlear/otologic/ear implant
- •Non-removable prosthesis
- •Implanted shunts/catheters
- •Certain intrauterine devices
- •Tattooed makeup
- •Body piercings that cannot be removed
- •Metal fragments
- •Wire sutures or metal staples
- •Factors that reduce MR image quality and interpretability (only an exclusion for patients participating in the brain MRI portion of this research):
- •Dental braces or other non-removable devices (e.g., retainers)
- •Prior brain surgery
- •Known brain MRI abnormality that in the investigator's opinion will significantly impact MRI data
- •Sensory disorders that in the investigator's opinion might affect perception of cutaneous thermal stimuli (e.g., peripheral neuropathy) (only an exclusion for patients participating in the neurophysiology studies)
- •Pregnancy
- •Breastfeeding
- •History of myocardial infarction, stroke, transient ischemic attack, unstable angina, coronary artery bypass surgery, or other revascularization procedures within 12 months prior to screening.
- •Not willing to use a reliable form of contraception (for women of childbearing potential) through 16 weeks after the last dose of erenumab. Acceptable methods of birth control include not having intercourse, hormonal birth control methods, intrauterine devices, surgical contraceptive methods, or two barrier methods (each partner must use a barrier method) with spermicide. A reliable form of contraception must be started prior to or at the time of starting the run-in phase. Not being of childbearing potential is defined as any woman who is post-menopausal by history, defined as:
- •At least 55 years of age with cessation of menses for 12 or more months; OR
- •Younger than 55 years of age but no spontaneous menses for at least 2 years; OR
- •Younger than 55 years of age and spontaneous menses within the past 1 year, but currently amenorrheic (e.g., spontaneous or secondary to hysterectomy), AND with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels at least 40 IU/L) or postmenopausal estradiol level (less than 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved; OR
- •Underwent bilateral oophorectomy; OR
- •Underwent hysterectomy; OR
- •Underwent bilateral salpingectomy.
- •Currently or within 90 days prior to screening: received treatment in another drug study or an investigational device study
- •Has previously received any CGRP ligand or receptor targeted monoclonal antibody
研究组 & 干预措施
Erenumab
140 mg erenumab
干预措施: Erenumab (Drug)
Placebo
placebo comparator
干预措施: Placebo (Other)
结局指标
主要结局
Change in the Number of Days Experiencing Moderate-to-Severe Headaches
时间窗: Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported
The number of days where subjects experienced moderate-to-severe headaches. This was measured at baseline, 9, 10, 11 and 12 weeks after administration of first dose of erenumab 140 mg or placebo. The change from baseline to week 12 is reported.
次要结局
- Responder Rate(Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported)
- Chronic Headache(Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported)
- Change in the Headache Impact Test (HIT-6)(Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported)
- Change in the Number of Days Where Acute Treatment Was Administered to Relieve a Headache(Baseline, 9, 10, 11 and 12 Weeks, change from baseline to week 12 reported)
研究者
Todd J. Schwedt
Principal Investigator
Mayo Clinic