Nurse Intervention Trial: The Evaluation of Usefulness of a Headache Nurse
Phase: NA
Conditions: Migraine, Chronic Tension-Type Headache, Cluster Headache, Hemicrania Continua
Sponsor: Norwegian University of Science and Technology

Cover page 
 
Short title: Nurse intervention Trial  
Full title: Nurse Intervention Trial: The Evaluation of Usefulness of a 
Headache Nurse 
Approval Number of Regional Committee for Medical Research:  
2023-554940  
Protocol Date: November 11. 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
1.1 Introduction 
Patients with headaches assessed in specialized healthcare who are prescribed medication 
would benefit from follow-up visits to evaluate if the prescribed treatment has been used 
and if it is effective. In practice, limited outpatient capacity with long waiting lists and 
delayed follow-up visits will limit the benefits of such planned follow-up. By utilizing nurses 
with expertise in headaches, the quality of follow-up care in specialized healthcare can be 
improved. Such task delegation between different healthcare professions has already been 
established in many clinical departments However; the potential benefit has not been 
documented in clinical randomized studies, as is the case, for example, with epilepsy nurses 
(1). 
For headaches, the majority of previous studies have focused on the benefits of headache 
nurses in primary healthcare (2-5). Few previous studies have assessed the benefits of 
headache nurses in specialized healthcare. A retrospective study conducted in the 
Netherlands showed that more patients with medication-overuse headache successfully 
discontinue pain medication in the group receiving close follow-up from headache nurses 
compared to the group without such follow-up (6). However, randomized studies for 
headache nurses are lacking. Quality depends on accurate diagnosis, personalized 
treatment, effective alternatives, patient information, and measurable treatment outcomes 
documented with headache diaries. Most neurological departments in Norway lack 
dedicated headache nurses. A randomized prospective study could provide evidence for the 
inclusion of headache nurses in more departments. 
A high quality of follow-up for headache patients in specialized healthcare depends, among 
other things, on accurate diagnosis, individualized treatment with effective and safe 
alternatives, providing good information to patients, and measurable endpoints of initiated 
treatment documented through the maintenance of a headache diary (7-9). The majority of 
the 18 different neurological departments in Norway currently do not have a dedicated 
headache nurse. Better justification for including headache nurses in more departments may 
result if a randomized prospective study demonstrates improved treatment of headache 
patients with the involvement of headache nurses. 
This randomized prospective study will focus on headache patients initiating preventive 
treatment, where the treating physician identifies a need for follow-up visits in specialized 
healthcare. The study will clarify whether the implementation (compliance) and overall 
satisfaction of the patient are better with follow-up by a headache nurse compared to 
standard follow-up. 
 
2.1. Utility  
This study will clarify the effectiveness of two different follow-up strategies for headache 
patients and thus contribute to increased quality of treatment in specialized healthcare. We 
aim to document whether the implementation of initiated treatment and overall satisfaction 

for headache patients improves with the follow-up by a headache nurse compared to 
standard follow-up. An optimized follow-up strategy will also be beneficial for individual 
headache patients being assessed in specialized healthcare. The results of the study will have 
implications for how specialized healthcare should be best organized for headache patients 
initiating preventive treatment. 
3.1. Problem Statement and Objectives  
The main objective is to compare the implementation and satisfaction of initiated treatment 
for patients with a primary headache diagnosis who receive follow-up from a headache 
nurse in the initial phase after starting new treatment, compared to standard follow-up 
where both groups are offered a check-up in specialized healthcare after approximately 3 
months. Among the sub-goals in the study is the time to achieve at least a 30% response to 
treatment relative to the group to which the patients are randomized.  
4.1 Methods 
This is an open randomized controlled follow-up study to assess the utility of a headache 
nurse. Eligible for inclusion in the study are headache patients who have been assessed by a 
neurologist in specialized healthcare and who, during the consultation, have received a 
definitive primary headache diagnosis and a need for preventive treatment. After 
completing the initial consultation, eligible patients will receive oral and written information 
and an invitation to participate. 
Potential patients suitable for this study must have undergone a regular consultation with a 
neurologist before. This consultation includes neurological and somatic examinations, 
diagnosis of the type of headache based on medical history, review of a completed headache 
diary, and any additional conducted examinations. The consultation will also involve an 
assessment of the possible initiation of preventive treatment. A selection of these patients 
will be prescribed electronic prescriptions for at least one previously untried type of 
preventive medication. During the consultation, patients will receive oral and written 
information about the dosage and expected possible side effects of the preventive 
medication. Those eligible for beta-blocker initiation will undergo an electrocardiogram 
(EKG) after the consultation. After completing the consultation, eligible patients will receive 
written and oral information about the study.  
Those who do not wish to participate will be referred back to their general practitioner for 
further follow-up, with the possibility of a new referral to specialized healthcare if needed. 
Those who provide consent to participate will, during subsequent registration with the 
secretaries at the neurological outpatient clinic immediately after the consultation, be 
randomized to one of two follow-up options (A or B) for further monitoring in the coming 
months until the scheduled follow-up, set at approximately 3 months, or later if there is a 
shortage of available appointments. 
Group A will be followed up by a headache nurse through telephone consultations at least 
two occasions shortly after the initiation of preventive medicine. Participants in this group 

will be invited to a planned final follow-up appointment after approximately 3 months with a 
neurologist, or later if there is a shortage of available appointments. 
Group B will have patient-managed follow-up with a planned final follow-up appointment 
after approximately 3 months with a neurologist. Participants will pick up the prescribed 
medication and contact their general practitioner or the neurological outpatient clinic by 
phone if they need advice from a neurologist. 
Randomization and storage of research data will be done electronically by eFORSK, where all 
involved study personnel will have a personal login to eFORSK. Training will be provided 
before the study commences. The complete questionnaire, consent, and participant list with 
ID numbers and CV for study personnel will be kept by the project leader in a locked cabinet. 
All included patients will be instructed to keep a continuous digital headache diary tailored 
for this study, which will be downloaded on their mobile phones via a dedicated application 
called "Brain Twin." 
At the start of the study, the physician conducting the consultation will fill out a concise form 
with headache diagnosis and general health, which will be reflected in the eFORSK. During 
follow-up consultations for groups A and B, any side effects and the effectiveness of the 
initiated treatment will be assessed through a review of the headache diary. For those using 
Valproate, blood tests will be taken after initiation. 
 
Inclusion criteria  
 Women and men aged 18 and older with one of the following headache diagnoses 
based on the International Classification of Headache Disorders, third edition 
(ICDH3): G44.1 Chronic tension-type headache and/or G43 Episodic and chronic 
migraine, G44.0 episodic and chronic cluster headache, G44.8; Hemicrania Continua 
 Overuse of attack medication consistent with the diagnosis of medication overuse 
headache does not exclude inclusion. 
 Indication for preventive medication where there is at least one alternative with the 
need for follow-up assessment of effectiveness. 
 
Exclusion criteria  
 Uncertain headache diagnosis. 
 Need for further investigation after the initial consultation. 
 Lack of understanding of information provided in Norwegian, both verbally and in 
writing. 
 Inability to keep a digital headache diary. 
 Need for further investigation or treatment of other comorbid conditions requiring 
follow-up in specialized healthcare. 
 Treatment with Onabotulinumtoxin A or Calcitonin-gene-related Peptide (CGRP) 
inhibitors given with tree months intervals 
 
Endpoints 
Primary endpoint: "Compliance": The number of participants who have carried out the trial 
as prescribed, defined as a minimum duration of two (2) months of the trial. 

 
Secondary endpoints:  
1. Number of days from inclusion to at least a 30% reduction in moderate to severe 
headache frequency compared to the frequency in the last month before the initial 
consultation. 
2. "Compliance" with headache diary: The number of participants with a completed 
headache diary. 
3. Number of responders measured by headache days (≥50% reduction in headache days 
compared to the corresponding registration before the first consultation). 
4. General satisfaction (1-4 scale from the fourth version of the Trøndelag Health study 
(HUNT4). 
5. Number of professional inquiries recorded about included study patients from either 
headache nurse or general practitioner directed to the responsible neurologist. 
 
Power calculation and analyses 
 Experiences from four previously conducted treatment studies on migraines with a duration 
of 30-48 weeks (10) showed a dropout rate of 10% of participants. During 3-5 months of 
follow-up, an expected dropout of a maximum of 15% is anticipated. In this two-armed 
parallel study, it is therefore preferable to include 200 patients in each arm (total of 400 
patients) (alpha 0.05, 80% power) if one wants to detect a difference in compliance of 15% 
between follow-up by a headache nurse and standard follow-up (e.g., compliance of 45% 
versus 30%). 
The null hypothesis is that there is no difference in compliance between the groups 
regardless of the type of follow-up (non-inferiority). By choosing a significance level of 0.05 
and 80% power, with a non-inferiority margin of 15%, 162 participants will be required in 
each group. By including 200 patients in each arm, the study will have sufficient statistical 
power to potentially conclude whether there is no difference in compliance between the 
groups. 
The primary endpoint will be analyzed using the chi-square test. The difference between the 
groups will be defined as statistically significant with a p-value <0.05. 
4.2. Organisation and collaboration 
This study is a collaborative project between the Neurology Clinic at St. Olav's Hospital and 
the Norwegian Centre for Headache Research (NorHead), Department of Neuromedicine 
and Movement Science, Norwegian University of Science and Technology (NTNU). 
Project leader Knut Hagen is a professor of Neurology and has been affiliated with the 
National Competence Service for Headaches for 15 years, combined with a position as a 
consultant involved in the assessment and follow-up of headache patients since 2005. He is 
currently the academic leader for the establishment of a new national quality register for 

severe primary headaches, along with a position as a medical advisor at the Clinical Research 
Unit, Central Norway, St. Olav's Hospital 
4.2.1 Other collaborating hospitals 
Oslo University hospital and Haukeland University Hospital  
4.3. Timeline 
The study is approved by the Regional Ethics Committee (REK) in January 25, 2023. The 
inclusion of the required number of patients and the completion of the follow-up period will 
likely be finished within 3 years (in the end of 2026). 
4.4 Publication plan 
Study results will be published in an international journal that allows for open access. Results 
will also be communicated to healthcare institution leadership, the healthcare system, and 
the department, as well as in understandable formats for newspapers, digital media, and 
blogs in collaboration with user representatives. 
4.5 Budget 
Financial support has been granted by the Joint Research Committee for the period 2023 to 
2025. This includes funding for a nurse in a 50% position. The infrastructure of the 
Norwegian Centre for Headache Research (NorHead) will be used for the involvement of 
study personal from Oslo University hospital and Haukeland University Hospital.  
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