We aim to conduct a pragmatic, multicentre, randomised clinical trial, assessing the effectiveness of manual therapy (MT) compared to usual GP care in patients with CTTH. We have used the guidelines of the International Headache Society (IHS) for the design of randomised clinical trials for headache to develop the randomisation procedure, outcome measurements and statistical analysis.[21
] The procedures and design of this study are approved by the Medical Ethics Committee of the VU University Medical Center in Amsterdam, The Netherlands. (Trial registration number TR 1074)
Participating primary healthcare centers and GPs in an urban area in the Netherlands, will invite patients with headache to participate in the trial.
Patients between 18 and 65 years of age are invited if they have CTTH according to the classification of headaches of the IHS [22
]: headache occuring on at least 15 days on average per month for a period of more than 3 months (≥ 180 days a year) and lasts for hours or may be continuous. The headache has at least one of the following characteristics: 1. bilateral location, 2. pressing/tightening (non pulsating) quality, 3. mild or moderate intensity, not aggravated by normal physical activities such as walking or climbing stairs; and both of the following: 1. no more than one of photofobia, phonophobia or mild nausea, and 2. neither moderate or severe nausea nor vomiting. Participants should be able to read and write Dutch.
Exclusion criteria include reumatoid arthritis, suspected malignancy, pregnancy, intake of either triptans, ergotamines or opioids on ≥ 10 days/month or simple analgesics on ≥ 15 days/month on a regular basis for ≥ 3 months, and having received manual therapy treatment in the 2 months before enrolment into the study.
After the GP has seen a patient with CTTH the patient receives an information letter about the trial. If the patient is willing to participate after reading the information he or she can contact the research centre. A researcher will screen interested patients by telephone and make an appointment to check inclusion and exclusion criteria, and complete the informed consent procedure. After written informed consent has been obtained, the baseline measurement is carried out. The design of the trial is explained in Figure .
Flow chart, representing the design of the trial on Chronic Tension Type Headache (CTTH).
Table shows the outcome measures and the time points at which they are assessed. At baseline we will collect additional information on demographic variables including age, gender, date of birth, education and occupation. The patient will also be asked to score expectations regarding the effectiveness of treatment on a 7-point rating scale (no result at all to very good result). In a standardised history taking procedure including the two-week headache-diary, the diagnosis of CTTH according to the diagnostic criteria of the IHS guideline will be confirmed.[22
Randomisation will take place after baseline measurement by the research assistant. Before the start of the trial a random sequence has been composed using computer-generated random numbers. Allocation is carried out by the research assistant who has not been informed about the random sequence, by giving the patient a numbered and sealed envelope.
The patient will open the envelope in the presence of another independent administrative assistant, who will subsequently make an appointment for the first treatment session either by the patient's own GP, or by one of the participating manual therapists.
GPs and manual therapists cannot be blinded for treatment allocation, but will not be informed about the results of outcome measurements. The research assistant is kept blind for the patient's treatment allocation.
Data collection and administration will by carried out by an independent data assistent. The researcher is involved in the statistical analysis, but the analysis and interpretation of the findings will be audited and verified by an independent statistician.
Patients will be treated by the GP according to the national clinical guideline for the management of headache [5
]. According to this guideline the GP will provide information, reassurance and advice and will discuss the benefits of lifestyle changes. If necessary, GPs may prescribe analgesics or non- steroid anti-inflammatory drugs (NSAID) or change current pain medication.
Manual Therapy intervention
MT treatment will include a combination of mobilisation of the cervical and thoracic spine, exercises and postural correction based on the management of cervicogenic headache. [23
] Spinal mobilisations will consist of low and/or high-velocity cervical and thoracic joint mobilization and manipulation techniques. Therapeutic exercises consist of low-load craniocervical muscle endurance exercises and correction of sitting and standing posture. The participating MT's are registrated MT's and member of the national association of manual therapists. They have an average experience of 10 years as manual therapist and have completed the McKenzie B-course on the cervical spine. In two meetings the MTs have been trained in the treatment protocol, they have received a manual and patient-booklets with home exercises.
Depending on the patient's condition the MT can decide what type of techniques and exercises will be selected from the protocol. The MT will make a report of the treatment modalities used in each session.
The MT intervention is restricted to a maximum of 9 sessions (each 30 minutes) in 8 weeks after randomisation.
Primary outcome measures
The follow-up measurements will take place by a blinded research assistant immediately after the 8 weeks treatment period and after 26 weeks (long term follow-up). Two weeks before each measurement the patients receive and complete a two-week headache diary. The primary outcome measures are 1) the frequency of days with headache, and 2) use of pain medication (no. of doses NSAIDs or simple analgesics). Registration over a two week period is considered to be sufficient.[24
Secondary outcome measures
The secondary outcome measures include:
* Headache pain intensity measured on a 10 point numerical rating scale (0 = no pain, 10 = most severe pain).
* The impact of headache on daily life will be scored by the patient using the Headache Disability Inventory (HDI) and the Headache Impact Test-6 (Hit-6). The HDI includes 25 questions on physical and emotional functioning with three possible response options: no = 0 points, sometimes = 2 points, yes = 4 points. A total score is computed by summating all scores, resulting in an individual HDI score ranging from 0 (no disability) to 100 (severe disability). A decrease in the total HDI of ≥ 16 points is considered to be a significant improvement. The test-retest reliability of the total score has been shown to be adequate (Pearson r
0.76 for 1 week; r
= 0.83 for 6 weeks) [25
* The Headache Impact Test (HIT-6) consists of 6 items (pain intensity, social functioning, role functioning, vitality, cognitive functioning and psychological distress) each with 5 response options; never: 6 points, rarely: 8 points, sometimes: 10 points, very often: 11 points, always: 13 points, with a total score ranging from 36 to 78 points. Internal consistency (Cronbach alpha: 0.89) and test-retest reliability (ICC ranging from 0.78 to 0.90) have been demonstrated to be good.[26
] The HIT-6 is able to differentiate between mild, moderate and severe headache. A between-group difference in HIT 6 change score of 2.3 points over time among patients with chronic daily headache reflects improvement in headache that may be considered to be clinically significant. [27
* The active range of movement in flexion, extension, right and left rotation and right and left lateroflexion of the cervical spine with the patient in a seated position will be measured by the research assistant with the CROM-device. The intra- and intertester reliability have been shown to be good (ICC. > 0.80). [28
* Algometry on the trapezius descendens and the suboccipital muscle will be performed with a Wagner FDK algometer with a 3.0 kg/cm pressure at four points at the left and right side: two points on the upper trapezius muscle and two points on the suboccipital muscle. Patients will rate the severity of pain on a 0–10 point NRS scale (0 = no pain, 10 most severe pain). Scores for each pressure point will be summated into a total score ranging between 0 and 80 points. Mechanical pressure algometry has been described by several authors as a valid measurement for pain pressure treshold for the trapezius muscle and has a good to excellent intertester- (ICC 0.70–0.91), intratester reliability (ICC 0.84–0.88) and a intra-individual coefficient of variation of 18.5% at 1 week test-retest. [29
* Endurance of the neck flexor muscles will be scored as the number of seconds the patient can raise his head from the table when lying on his/her back. In a study of the neckflexor endurance test among subjects without neck pain Harris et al. reported good to excellent intratester reliability (ICC 0.82–0.91) and moderate intertester reliability (ICC 0.67–0.78).[32
* A lateral digital picture with a digital HP R707.5 camera will be taken in a seated and standing position to measure the craniocervical angle. Recently van Niekerk et al. evaluated the criterion validity of photographic measurement compared with a digital radiographic device (LODOX) for assessing the craniocervical angle in sitting position among high school students (Pearson r
] The reliability of photographic measurement of the craniocervical angle has been reported to be good in two studies(ICC >0.86). [33
* Additional use of health care resources (including GP, psychologist, physiotherapist, acupuncture) will be reported by the patient at 26 week follow-up by completing a checklist. The patient will also be asked to report perceived improvement following treatment on a 7 point scale. (0 = much worse to 6 = much better).
In a pilot study the 2 weeks headache diary showed an average of 11 days with headache in both treatment groups at baseline. After 8 weeks the frequency of days with headache in the GP group was reduced to 7 days, in the MT group to 3 days. In the full trial we aim to detect a difference in reduction of at least 3 days (SD 5) between both groups. To detect this difference with a one-sided significance level of 0.05, and power of 0.80 we have to include at least 35 patients in each treatment group. The participants in the pilot study reported taking on average 2 doses of NSAID or analgesics per 2 weeks. With a sample size of 35 patients per group we can detect a difference of at least 0.5 (SD 0.8) doses per 2 weeks between the groups. With a calculated loss of participants in the full trial of 15%, this trial attempts to enroll forty-two patients with CTTH in each treatment groups (GP, MT).
Baseline comparability will be investigated by descriptive statistics to examine whether randomisation was successful. For each patient, the change between baseline and follow-up will be calculated for all primary and secondary outcome measures. The statistical analysis will be performed according to the intention-to-treat principle.
Between group differences and 95% confidence intervals will be calculated, and tested using the Student t-test in case of normal distributions. Non paramaratric testing will be used for non-normal distributions. In addition, a per-protocol analysis will be performed, analysing only those patients with no serious protocol deviations. Comparing the results of the intention-to-treat and the per-protocol analysis will indicate if and to what extent protocol deviations might have influenced the results. Multivariate regression analysis will be conducted to examine the potential influence of differences in baseline characteristics on outcome.
If results on primary outcomes show normal distributions we will compute effect sizes (standardised mean differences) as the mean difference between groups over the pooled standard deviation. Effect sizes will be rates as follows: small (0.2–0.5), medium (0.5–0.8) or large (>0.8).
Feasibility of the study design
A pilot study was conduced between June 2006 and December 2006 to evaluate the feasibility of the measurements, randomisation-procedure and treatment protocols (33). The recruitment of participants for this pilot-study took place in two primary health-care centers in The Netherlands. A total of 20 patients were randomised to either the GP or the MT intervention group. Thirty-one patients who had a strong preference for the manual therapy intervention and could not be randomised were asked to participate in a parallel cohort-study. In this study similar baseline and follow up measurements were conducted.
The results of the pilot study showed that the procedures were feasible. The research-assistants, general practitioners and manual therapists reported having no problems to adhere to the guidelines and protocols for measurements and treatment. In order to include a total of 80 patients over a period of one year, 32 GPs and 4 MTs have been recruited to participate in the full trial.