Clinical trial NCT04693533: Fremanezumab, Migraine and Sleep
Official title: Fremanezumab, Migraine and Sleep
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Migraine Disorders
Sleep Disorder
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Teva Pharmaceuticals USA
First posted: 2021-01-05
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The main goal of this study is to determine whether there is a relationship between fremanezumab's ability to prevent migraine and improved sleep quality in migraine patients (fremanezumab is a FDA-approved humanized CGRP monoclonal antibody for the treatment of migraine).

This is a within-person study design that examines treatment effects (changes) using high-resolution assessments. To complete the study, each participant will be observed using daily assessments of migraine and sleep outcomes before treatment (baseline: 0 to 30 days), and at 1, 2, and 3 months after treatment (injection 1: days 31-60, injection 2: days 61-90, injection 3: days 91-120). In essence, this creates an interrupted time-series design where repeated interventions are introduced at fixed intervals.

Detailed description: The study involves 5 visits to the headache clinic:

In clinic visit 1 (day 0), subjects will learn about the study and if they agree to participate, will be consented and screened for eligibility. Those deemed to be eligible will be asked to fill a headache questionnaire and then taught how to fill at home a daily e-diary for sleep and a daily e-diary for headache.

In clinic visit 2 (day 30), subjects will return to the headache clinic to review their e-diaries and receive the first treatment. The treatment is 225 mg (dissolved in 1.5 ml solution) fremanezumab. Fremanezumab is a monthly dosed anti-CGRP mAb injection.

In clinic visit 3 (day 60), we will review participants' headache and sleep diaries 1 month after receiving the 1st injection and administer the 2nd injection. This appointment will be conducted by either one of the study physicians or the study nurse.

In clinic visit 4 (day 90), we will review participants' headache and sleep diaries 1 month after receiving the 2nd injection and and administer the 3rd injection. This appointment will be conducted by either one of the study physicians or the study nurse.

In clinic visit 5 (day 120), participants will return to the headache clinic to summarize their experience, review their 120-days e-diaries, and provide any feedback they may have about their experience with fremanezumab.

Assessments of headache and sleep:

At screening (visit 1), headache severity and impact will be assessed based on patients' interviews and HIT-6. Sleep quality will be assessed using the Insomnia Severity Index. (https://cbtscience.files.wordpress.com/2014/02/insomniaseverityindex.pdf).

On days 30, 60, 90 and 120, baseline and treatment impact on headache and sleep will be assessed using the Headache e-diary and the consensus sleep diary \[Carney et al., (2012) The consensus sleep diary: Standardizing prospective sleep self-monitoring, Sleep Vol.35, No.2, pp.287-302\], the latter of which captures total sleep time, sleep latency, wake after sleep onset, number of awakenings, quality, sleep efficiency, and trouble staying awake.

Eligibility criteria: Inclusion Criteria:

* Between the ages of 18 and 65 years
* Been previously diagnosed with migraine (with or without aura), in accordance with the ICHD-3 criteria
* Experiences between 10 to 25 headaches days per month (during the last 3 months), with at least 8 of them being migraine days during which the migraines lasted more than 4 hours if untreated
* Onset of migraine at age 50 years or younger
* Agrees to refrain from initiating or changing the type, dosage, or frequency of any prophylactic medications for indications other than migraine that may interfere with the study objectives (e.g., antidepressants, anticonvulsants, beta-adrenergic blockers, etc.)
* Able to provide written informed consent
* Scoring 10 or higher on the Insomnia Severity Index (8-14 = subthreshold insomnia, 15-21 = clinical insomnia of moderate severity, 22-28 = clinical insomnia of severe severity)

Exclusion Criteria:

* -
* Currently on a regimen of 1 or more migraine preventative therapy
* Other significant pain problem (e.g., cancer pain, fibromyalgia, other head or facial pain disorder) that may confound the study assessments
* Known or suspected severe cardiac disease (e.g., symptomatic coronary artery disease, prior myocardial infarction, congestive heart failure)
* Known or suspected cerebrovascular disease (e.g., prior stroke or transient ischemic attack, symptomatic carotid artery disease, prior carotid endarterectomy or other vascular neck surgery)
* Abnormal baseline electrocardiogram (ECG) within the last year (e.g., second or third-degree heart block, prolonged QT interval, atrial fibrillation, atrial flutter, history of ventricular tachycardia or ventricular fibrillation, clinically significant premature ventricular contraction)
* Uncontrolled high blood pressure (systolic \>160 mm HG, diastolic \>100 mm Hg) after 3 measurements within 24 hours
* Known history or suspicion of secondary headache
* Known history or suspicion of substance abuse or addiction (within the last 5 years)
* Currently using marijuana (including medical marijuana) or has used marijuana (including medical marijuana) or cannabidiol oil within the last 1 year
* Currently takes simple analgesics or NSAIDs \>15 days per month or triptans, ergots, or combined analgesics \>10 days per month for headaches or other body pain
* Currently takes prescription opioids for headaches or body pain
* Undergone nerve block (occipital or other) in the head or neck within the last 3 months
* Received botulinum toxin or anti-CGRP-mAb injections within the last 6 months
* Nursing, pregnant or thinking of becoming pregnant during the study period, or of childbearing years and unwilling to use an accepted form of birth control
* Participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days
* Belongs to a vulnerable population or has any condition such that his or her ability to provide informed consent, comply with the follow-up requirements, or provide self-assessments is compromised.
* A relative of or an employee of the Investigator or the clinical study site
* Psychiatric or cognitive disorder and/or behavioral problems that, in the opinion of the clinician, may interfere with the study
* History of claustrophobia
* Diagnosis of obstructive sleep apnea or restless legs syndrome
* BMI of 30 or greater
* Daily use of sleep-promoting drugs. These include eszopiclone; zaleplon; zolpidem; benzodiazepines (estazolam, flurazepam, quazepam, temazepam, triazolam); barbiturates (amobarbital, amobarbital-secobarbital, chloral hydrate); doxepin; quetiapine; ramelteon; trazodone; suvorexant; lemborexant; OTC nighttime meds (doxyalamine; diphenydrame); and melatonin.

Primary outcomes:
measure: Fremanezumab and sleep
timeFrame: 4 months
measure: Fremanezumab and migraine
timeFrame: 4 months
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: BIDMC Headaceh Clinic
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Sait Ashina, MD
role: PRINCIPAL_INVESTIGATOR
References: