Efficacy and Central Mechanisms of Electroacupuncture for... | NCT06802471

Description Module

Detailed Description

This is a multicenter, stratified, randomized, sham-controlled clinical trial. 120 eligible participants will be randomly allocated into electroacupuncture (EA), sham electroacupuncture (SEA), in a 1:1 ratio, which was divided into two phases

Phase 1 :

1. The EA group will receive 30 electroacupuncture treatments over an 12-week period, while the SEA group will receive sham electroacupuncture treatments with non-penetrating needling.

The two control groups are matched to the MOH patient group by gender and age for recruitment when the planned MOH patient enrollment was nearly 80% complete, and 20 patients in each group will be included, for a total of 40 patients.

Health education will be provided to participants in each group. The primary outcomes will be the changes of headache days per month from baseline after 12 weeks of treatment; The secondary outcomes will be as follows: The change from baseline in the number of headache days per month was also evaluated after 4 weeks of treatment, 8 weeks of treatment, 24 weeks of follow-up, and 36 weeks of follow-up; The proportion of responders, Headache Days per month, average daily headache time, headache Severity, average daily moderate-to-severe headache days, average daily moderate-to-severe headache time, Days with acute medication, Doses taken monthly, Severity of Dependence Scale, Headache Impact Test, EQOL-5D-5L, Hospital Anxiety and Depression Scale, Patients'expectation of the acupuncture efficacy, The Patient Global Impression of Change, The patient blinding assessment, Brain MRI Data Analysis and Multi-omics Analysis; The central randomization and data collection will be conducted by an electronic data management system.

Phase 2:

participants who adhere to the study protocol and complete the Week 36 follow-up will be considered to have completed the study. If the results of the first-phase trial demonstrate that electroacupuncture is superior to the control group, and the participants' willingness is confirmed, those willing to proceed will undergo the second-phase follow-up.

The second phase of follow-up was conducted at 1, 2, and 3 years after the end of treatment.These included whether the participant was lost to follow-up, headache diary (including headache frequency and medication use), recurrence of MOH, new comorbidities, and assessments using SDS, HIT-6, HADS, PGIC, and EQ-5D-5L.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
elecrtoacupuncture group (EA group)	Experimental	Participants will be treated by electroacupuncture. They will be treated 3 sessions a week for the first 6 weeks and 2 sessions a week (once every 2-3 days) for the next 6 weeks. The total course of treatment was 30 times for 12 weeks, each electroacupuncture treatment session for patients will be 30 minutes in duration. All the participants will be accepted usual care: Health education is provided in three aspects: lifestyle changes, behavioral therapies and MOH self-management. Basic treatment: Throughout the study period, patients could continue to use their previously overused symptomatic medications as usual. MOH patients are required not to change the type, single dose, or formulation of acute medications. However, they are allowed to increase or decrease the frequency or total amount of use based on their pain condition. Any use of new medications must be accurately documented.	Device: electroacupuncture
Sham elecrtoacupuncture group (SEA group)	Sham Comparator	Participants will be treated by sham elecrtoacupuncture. They will be treated 3 sessions a week for the first 6 weeks and 2 sessions a week (once every 2-3 days) for the next 6 weeks. The total course of treatment was 30 times for 12 weeks, each electroacupuncture treatment session for patients will be 30 minutes in duration. All the participants will be accepted usual care: Health education is provided in three aspects: lifestyle changes, behavioral therapies and MOH self-management. Basic treatment: Throughout the study period, patients could continue to use their previously overused symptomatic medications as usual. MOH patients are required not to change the type, single dose, or formulation of acute medications. However, they are allowed to increase or decrease the frequency or total amount of use based on their pain condition. Any use of new medications must be accurately documented.	Device: Sham electroacupuncture
Control group 1（CG 1）

Interventions

Name	Type	Description	Arm Group Labels	Other Names
electroacupuncture	Device	The supine position, the local skin of the acupoints was routinely sterilized, and the selected acupoints were pasted with Acupuncture auxiliary device. The main acupuncture points are DU20, bilateral EX-HN5, ST8, GB20, GB20, LI4, LR3, ST40. Select compatible acupoints based on the patient's accompanying symptoms: 1.Discomfort in the neck: EX-B2 of Cervical 3-4; 2.Emotional anxiety, depression or sleep disorders: GV29, HT7; 3.Stomach or abdominal discomfort: CV12, ST25 and CV6. The disposable acupuncture needles and the electronic acupuncture treatment instrument SDZ-V nerve and muscle intimulator both manufactured by Suzhou Medical Appliance Factory Co., Ltd., China.The specifications of acupuncture needles are Φ0.30×25mm, Φ0.30×40mm, Φ0.30×50mm. The needles will be inserted into the skin of acupuncture points and manipulated manually by using the techniques such as lifting, thrusting, and twirling, until the internal compound sensation known as deqi.

Measure	Description	Time Frame
Change in the number of headache days	Change from baseline in headache days per month	At the end of week 12 after randomization.

Measure	Description	Time Frame
Change in the number of headache days	Change from baseline in headache days per month	At the end of week 4, week 8 after randomization; at week 24, week 36 of the follow-up period,
The proportion of responders

Measure	Description	Time Frame
The proportion of patients with < 15 headache days per month		At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
The proportion of patients with headache free days per month		At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,

Eligibility Module

Eligibility Criteria

Inclusion Criteria for Patients with MOH:

Meet the diagnostic criteria of MOH in ICHD-3;
A history of migraine (according to ICHD-3 criteria)/tension headache (TTH) (according to ICHD-3 criteria) for ≥12 months before screening;
Patients entered data from the electronic headache diary for at least 24 of the 28 days of the screening period (evidence of good adherence to the electronic headache diary);
Prospectively collected data from the electronic headache diary during the screening period met the following criteria: 15 or more headache days per month; Regular overdose of acute or symptomatic headache medications meets the diagnostic criteria for MOH；
Headache diagnosed before the age of 50 years;
Patients had failed MOH withdrawal treatment (with medical documentation or specific physician confirmation of each treatment) on ≥1 occasions in the previous 3 years; Withdrawal treatment failure is defined as no significant reduction in headache frequency, duration and/or severity after withdrawal treatment; Or intolerable withdrawal reactions during withdrawal treatment; Or unable to quit treatment due to safety issues;
Aged between 18 and 80 years old;
Signed the informed consent and volunteered to participate in the study.
Patients who met the above 8 criteria were included in this study.

Exclusion Criteria for Patients with MOH:

Patients had a history or diagnosis of hypotensive headache, continuous hemiplegia, new daily persistent headache, or unusual migraine subtypes, such as hemiplegic migraine (sporadic and familial), ocular tension migraine, migraine with neurologic symptoms that were atypical of migraine aura (diplopia, altered consciousness, or prolonged duration). Other types of primary or secondary headache;
The presence of clinically significant pain syndromes that may be confusing (e.g., fibromyalgia, chronic low back pain, complex regional pain syndrome); Acute or active temporomandibular joint disorders;
The patient had an uncontrolled and/or untreated mental illness (e.g., severe depression and schizophrenia) for at least 6 months prior to the screening visit; Patients with a history of psychosis and/or mania within 5 years before screening were excluded;
The patient has any other medical condition whose treatment takes precedence over MOH treatment or may interfere with the study treatment or impair compliance with treatment;
Taking/using medications/stimulation devices that may affect headache (e.g., beta-blockers (atenolol, propranolol, metoprolol, etc.) due to headache or other reasons within 3 months before or during the screening period; Calcium channel blockers (flunarizine, benzothiazide, etc.); Antidepressants (amitriptyline, venlafaxine, duloxetine, etc.); Antiepileptic drugs (topiramate, sodium valproate, carbamazepine, etc); Angiotensin-receptor blockers (candesartan and lisinopril); Botulinum toxin; Gabapentin; Noninvasive vagus nerve stimulation, transcranial magnetic stimulation, peripheral trigeminal nerve stimulation; Biofeedback, health products; Occipital nerve block, other nerve block; Continuous infusion therapy, steroid reduction; Chiropractic therapy, physical therapy); Or treatment with injections (trigger point injections, extracranial nerve blocks or facet joint injections) on the head, face or neck;
The patient has a history of moderate or severe head or neck trauma, or other neurological or systemic diseases (such as epilepsy and dementia) that the researcher believes may affect the central nervous system function;
Patients have or have had one or more of the following conditions that were considered in the study to be associated with clinical symptoms: other neurological, pulmonary, hepatic, endocrine, gastrointestinal, hematologic, infectious, immunologic, or ocular conditions;
A history of substance or alcohol abuse (according to DSM-5® criteria) within 24 months prior to the screening visit;
During the screening or baseline visit, the patient has significant suicide risk (answers "Yes" to question 4 or 5 on the C-SSRS suicide ideation section, or answers "Yes" to any question regarding suicidal behavior at any time during the study on the C-SSRS);
Prophylactic treatment for headache was received 1 month before the screening visit;
One month before the screening visit, the patient had participated in a clinical study; Or had taken any medication for headache within the 5 plasma half-lives, whichever was longer, before the screening visit;
Severe uncontrolled disease such as cancer, uncontrolled cardiovascular disease, severe hepatic and renal insufficiency, or coagulopathy; Women who are pregnant or preparing to become pregnant;
Having known fear of acupuncture or having received acupuncture treatment within 8 weeks before enrollment;
In the judgment of the investigators, the patients have diseases or take drugs that may affect the assessment of the safety, tolerability, or efficacy of the trial, or affect the conduct or interpretation of the study.
Any one of the above items is excluded.

Inclusion Criteria for Patients with episodic migraine(Control group 1):

According to the ICHD-3 criteria, it met the diagnostic criteria of episodic migraine; With/without tension-type headache;
Headache days/month ≤6 days at enrollment;
The number of days/month of using analgesics at enrollment was ≤6 days;
Age between 18 and 80 years;
Be able to fill out a headache diary;
No previous history of drug abuse;
No obvious comorbidities pain, physical or mental disorders;
No alcohol or drug addiction;
No pregnancy, breastfeeding, or plans for pregnancy in the next 12 months;

Inclusion Criteria for Healthy Participants(Control group 2):

No headache or headache ≤2 days in the past 12 months at enrollment;
No more than 6 days/month of use of analgesics at enrollment;
Age between 18 and 80 years;
No significant comorbidities pain, physical, or mental disorders;
No organic, functional changes or systemic diseases that could cause headache;
No history of head or neck trauma;
No significant abnormalities in blood routine, biochemical tests, coagulation function, or urine routine in the past 12 months prior to enrollment;
No alcohol or drug addiction;
No pregnancy, breastfeeding, or plans for pregnancy in the next 12 months.

Nonrandomized patients with MOH:

●Participants who meet the MOH diagnostic criteria and fulfill the inclusion/exclusion criteria but decline randomization will be assigned to the non-randomized electroacupuncture group. These participants will receive electroacupuncture treatment directly, with no restrictions on the number of participants per center.

ID	Term
D020773	Headache Disorders
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases

ID	Term
D003131	Combined Modality Therapy
D013812	Therapeutics
D015670	Acupuncture Therapy
D000529	Complementary Therapies