针刺预防偏头痛远期疗效评价（续1）
MethodsStudy Population and ProtocolWe recruited patients who had migraine without aura from the outpatient unit of the Departments of Acupuncture and Neurology in 3 clinical centers: the teaching hospital of Chengdu University of Traditional Chinese Medicine (TCM), the First Affiliated Hospital of Hunan University of TCM, and the Affiliated Hospital of Chongqing Medical University. Migraine without aura was diagnosed according to the classification criteria of the International Headache Society.Patients who complained of recurrent headaches lasting 4 to 72 hours, unilateral headaches with pulsating quality, and also headaches aggravated by routine physical activity were recruited for further evaluation. Patients were enrolled in the study from October 2012 to September 2014. Patients were not reimbursed, but did receive free treatment. The protocol was approved by the local institutional ethics review boards and was performed in accordance with the Declaration of Helsinki and the Chinese version of the International Conference on Harmonization–Good Clinical Practice. The protocol was published previously and is available in the Supplement.The inclusion criteria were as follows: men or women 18 to 65 years old with initial onset of migraines prior to the age of 50 years; experience of acute migraine attacks at a frequency of 2 to 8 times per month 3 months before inclusion; experience of migraine attacks for at least 1 year; completion of a baseline headache diary; and provision of written, informed consent by the patients. Patients with any of the following conditions were excluded: headache caused by organic disorders (eg, subarachnoid hemorrhage, cerebral hemorrhage, cerebral embolism, cerebral thrombosis, vascular malformation, arteritis, hypertension, or arteriosclerosis); the presence of neurological diseases, immunodeficiency, bleeding disorders, or allergies; prophylactic headache treatment with drugs during the previous 3 months; pregnancy, lactation, or plans to become pregnant within 6 months; or involvement in other clinical trials. Randomization and Blinding
A total of 249 eligible patients were recruited and were randomly assigned at a 1:1:1 ratio to receive TA treatment or SA treatment, or to be place on a WL. Central randomization,
using an online or messaging system, was performed by the Brightech Magnsoft Data Services. Randomization sequence was generated in blocks of varying sizes and stratified by centers. The participants in the TA group and SA group were blinded, while those in the WL group were not. Acupuncturists could not be blinded to the treatment assignments given the nature of the interventions. Outcome assessors, data collectors, and statisticians were blinded to the treatment allocation.
Interventions
Electrostimulation generates an analgesic effect, as manual acupuncture does.All acupuncturists were trained for at least 5 years and licensed with at least 4 years of clinical experience. Patients in the TA group and the SA group received 20 sessions of electroacupuncture treatment (once per day for 5 consecutive days followed by a 2-day break), each lasting 30 minutes, for 4 weeks. Migraineurs were not allowed to take any prophylactic medications. In cases of intolerable headache, the patients were instructed to take ibuprofen (300-mg capsules with sustained release) as a rescue medication, and the usage of ibuprofen was documented in the headache diary. Four acupoints were used per treatment. All patients received acupuncture on 2 obligatory points, including GB20 and GB8. The 2 other points were chosen according to the syndrome differentiation of meridians in the headache region. The potential acupoints included SJ5, GB34, BL60, SI3, LI4, ST44, LR3, and GB40.The use of additional acupoints other than the prescribed ones was not allowed. We chose the prescriptions as a result of a systematic review of ancient and modern literature,consensus meetings with clinical experts, and experience from our previous study.Sterile, single-use filiform acupuncture needles, each with a length of 25 to 40 mm and a diameter of 0.25 mm, were used in the treatment. Acupuncturists applied therapy unilaterally by alternatively using the left and right acupoints. Each point was acupunctured to achieve the Deqi sensation (a sensation of soreness, numbness, distention, or radiating that indicates effective needling). The HANS acupoint nerve stimulator (model LH 200A;Han Institute, TENS, Nanjing, China) was used after needle insertion. The stimulation frequency was 2/100 Hz (alternating every 3 seconds), and the intensity varied from 0.1 to 1.0 mA until the patients felt comfortable. This stimulation method was optimal for obtaining an analgesic effect21 and was used successfully in our previous study. In addition, more details of the procedure have been published.The number of needles, electric stimulation, and duration of treatment in the SA group were identical in the TA group except that an attempt was not made to induce the Deqi sensation. Four nonpoints were chosen according to our previous studies.20,24 Patients in the WL group did not receive acupuncture from the beginning of the clinical trial but were informed that they would be provided with 20 sessions of acupuncture treatment for free after 24 weeks.
MeasuresData Collection
All patients were instructed to complete headache diary records every 4 weeks after inclusion. The headache diary documented the time of migraine onset, duration, severity (evaluated by the visual analog scale score), and rescue medication use. The frequency of migraine attacks over 24 weeks, migraine days, and the intensity of each attack were calculated every 4 weeks. At each follow-up, 2 blinded evaluators at each clinical center reminded patients by phone calls or text messages to return the headache diary to the trial offices via emails or to outpatient offices at follow-up visits.
Outcome Measures
The primary outcome was the change in the frequency of migraine attacks between baseline and 16 weeks after randomization. Secondary outcome measures included the number of days with migraine (migraine days), average headache severity, and medication intake every 4 weeks within 24 weeks. In addition, migraine-specific quality-of-life questionnaire (MSQ), and pain-related impairment of emotion (the Zung selfrating anxiety scale and Zung self-rating depression scale ) were assessed at baseline and at the 4-week visit. Researchers documented acupuncture treatment and reasons for dropouts during the study period. Acupuncture-associated AEs, including bleeding, subcutaneous hemorrhage, hematoma, fainting, serious pain, and local infection, were recorded at each treatment session.
Sample Size Calculation and Statistical Analysis
We designed our trial to determine whether there was a difference among the TA group, the SA group, and the WL group in terms of the frequency of migraine attacks. According to our previous study,18 we anticipated that the frequency of migraine attacks over 16 weeks would be 2.7 in the TA group and 3.7 in the SA group, considering a mean clinically relevant difference of 1.0 and a standard deviation (SD) of 1.81. With a 2-sided significance level of 5% and power of 90%, 70 participants per group would be required, as calculated by NQuery Advisor software (version 4.0; Statistical Solutions). With an estimated loss-to-follow-up rate of 15%, we planned to enroll 249 participants in the 3 groups, with 83 participants in each group.
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