Clinical trial NCT06802471: Efficacy and Central Mechanisms of Electroacupuncture for Medication Overuse Headache
Official title: Efficacy and Central Mechanism of Electroacupuncture for Medication Overuse Headache: a Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Medication Overuse Headache
Electroacupuncture
Lead sponsor: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
Sponsor class: OTHER
First posted: 2025-01-31
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Acupuncture is commonly used for the prevention of migraine and tension-type headaches, and has been found to be effective in reducing both the frequency and severity of these conditions. However, studies on acupuncture for medication overuse headache (MOH) are limited, and current research has not been able to determine whether its efficacy is due to the actual therapeutic effects of acupuncture or psychological benefits. To address this issue, the investigators have designed a clinical trial to evaluate the efficacy of acupuncture for MOH. In addition, the investigators will explore the regulatory effects of electroacupuncture on central mechanisms in MOH and conduct multi-omics analysis.

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.

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.

Primary outcomes:
measure: Change in the number of headache days
timeFrame: At the end of week 12 after randomization.
Secondary outcomes:
measure: Change in the number of headache days
timeFrame: At the end of week 4, week 8 after randomization; at week 24, week 36 of the follow-up period,
measure: The proportion of responders
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: The proportion of patients with at least 50% reduction in headache days per month
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: Change in mean daily headache duration
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: The proportion of patients with at least 50% reduction in mean daily headache duration
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: Change in headache severity score per month
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: The proportion of patients with at least 50% reduction in headache severity score per month
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: Change in the number of moderate and severe headache days per month
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: The proportion of patients with at least 50% reduction in the number of moderate and severe headache days per month
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: Change in mean daily duration of moderate and severe headache
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: The proportion of patients with at least 50% reduction in mean daily duration of moderate and severe headache
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: Change in number of days per month with acute medication for headache
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: The proportion of patients with at least 50% reduction in number of days per month with acute medication for headache
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: Change in total number of doses taken per month for headache
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: The proportion of patients with at least 50% reduction in total number of doses taken per month for headache
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: Change in Severity of Dependence Scale (SDS)
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: Change in Hospital Anxiety and Depression Scale (HADS)
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: Change in Headache Impact Test (HIT-6)
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: Change in Patient Global Impression of Change (PGIC)
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: Change in five-level version of EQ-5D (EQOL-5D-5L)
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: Patients'expectation of the acupuncture efficacy
timeFrame: At baseline
measure: The patient blinding assessment
timeFrame: Within 5 minutes after the completion of any week 12 treatment session
Other outcomes:
measure: The proportion of patients with < 15 headache days per month
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: The proportion of patients with headache free days per month
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: The proportion of patients with cured Medication Overuse Headache(MOH)
timeFrame: At the end of week 4, week 8 and week 12 after randomization; at week 24, week 36 of the follow-up period,
measure: The recurrence rate in patients with cured MOH
timeFrame: At week 24, week 36 of the follow-up period
measure: Brain MRI Data Analysis
timeFrame: At baseline and week 12 after randomization
measure: Single-Cell Omics Outcome Analysis
timeFrame: 1.EA group: At baseline and week 12 after randomization; 2.SEA group: at week 12 after randomization.
measure: Proteomic Outcome Analysis
timeFrame: At baseline and week 12 after randomization
measure: Metabolomics Outcome Analysis
timeFrame: At baseline and week 12 after randomization
measure: Change in mean daily headache duration
timeFrame: At week 60, week 108 and week 156 of the follow-up period.
measure: Change in mean daily duration of moderate and severe headache
timeFrame: At week 60, week 108 and week 156 of the follow-up period.
measure: Change in total number of doses taken per month for headache
timeFrame: At week 60, week 108 and week 156 of the follow-up period.
measure: Change in number of days per month with acute medication for headache
timeFrame: At week 60, week 108 and week 156 of the follow-up period.
measure: The recurrence rate in patients with cured MOH
timeFrame: At week 60, week 108 and week 156 of the follow-up period.
measure: Change in Severity of Dependence Scale (SDS)
timeFrame: At week 60, week 108 and week 156 of the follow-up period.
measure: Change in Hospital Anxiety and Depression Scale (HADS)
timeFrame: At week 60, week 108 and week 156 of the follow-up period.
measure: Change in Headache Impact Test (HIT-6)
timeFrame: At week 60, week 108 and week 156 of the follow-up period.
measure: Change in Patient Global Impression of Change (PGIC)
timeFrame: At week 60, week 108 and week 156 of the follow-up period.
measure: Change in five-level version of EQ-5D (EQOL-5D-5L)
timeFrame: At week 60, week 108 and week 156 of the follow-up period.
Locations:
city: Beijing
country: China
facility: Department of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences Guang´anmen Hospital
state: Beijing
Study officials:
affiliation: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
name: Weiming Wang, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: