Design of the study
The study is a randomised controlled trial (RCT). The Medical Ethical Committee of the VU University Medical Center in Amsterdam approved the study design, protocols, information letters to the patients and informed consent form.
The trial is conducted within 'the Diabetes Care System (DCS)', a managed care system that was implemented in The Netherlands, as described above. This care system has a well organised infrastructure with experienced medical assistants, diabetes nurses and dieticians and is therefore a suitable setting to implement a new therapy for patients with diabetes.
The source population consist of patients with type 2 diabetes of participating GPs. Selection criteria for the GPs are that they have a practice nurse and that they are part of the DCS. GPs will be informed about the study by one of the researchers (GN) and a diabetes nurse and are asked to participate. They have to sign an intention declaration to confirm participation.
Patients from the participating GPs, who are scheduled to visit the DCS for their annual visit, are sent an information letter on the study. This letter is announced in the telephone call that the reception of the DCS has with the patient to make an appointment for their annual visit at the medical assistant.
Patients visit the medical assistant for their annual physical examination of the DCS. The medical assistant checks eligibility of the patient for the study. Patients are eligible if they meet the following inclusion criteria: diagnosis of type 2 diabetes, between 40 and 75 years of age, able to understand the Dutch language in order to understand the study protocol, written informed consent and questionnaires, high risk for cardiovascular disease and diabetic complications. Patients are considered at risk if, according to measurements of the previous annual visit, HbA1c ≥ 7.0 % and/or body mass index ≥ 27.0 kg/m2 and/or the patient smokes. In addition, all newly diagnosed patients, who do not have annual check-up results available, are considered eligible, based on the fact that all new patients need to learn how to deal with their diabetes. If all inclusion criteria are met, the medical assistant explains the purpose of the study and patients are asked if they are interested in participation.
All patients must sign a written informed consent form. Subsequently, physical measurements are performed, which include body weight, waist circumference, blood pressure, and drawing of blood samples (to assess fasting blood glucose, HbA1c, total cholesterol, HDL-cholesterol and triglycerides). In addition, patients are given a self-administrated questionnaire to fill in at home, including questionnaires on physical activity, dietary intake, smoking status, determinants of behaviour according to the ASE-model, quality of life, depression, general health and patient satisfaction. The responsible GP is informed that the patient is participating in the study. During the study, GPs receive fax forms from the diabetes nurses and dieticians advising on required medication changes for a specific patient.
Patients are randomly assigned to either the intervention group, receiving CBT in addition to the managed diabetes care or the control group, receiving managed diabetes care only. Approximately three weeks after the visit to the medical assistant, patients are scheduled for either the first intervention or control session to the diabetes nurse and dietician.
Block randomisation is performed within the general practices in order to eliminate the influence of different treatments of general practitioners. From each general practice, half of the patients are randomised to the intervention group or the control group. The principle investigator (LMCW), who is not involved in the selection and treatment of patients, prepared a randomisation list using series of random numbers . Random permuted blocks of 4 patients are made to ensure equal distribution of patients for each general practice. The manager of the DCS, who is not involved in the patients' care, allocates the patient to one of the two groups by using the randomisation list. The flow of the patients is registered by the principal investigator (LMCW), according to a flow diagram recommended by the CONSORT statement . Reasons for withdrawal are registered by the medical assistant. Figure 1 shows the design of the study.
Patients, diabetes nurses and dieticians cannot be blinded to the intervention. The medical assistants are blinded as far as possible. They have close contact with the diabetes nurses and dieticians within the DCS and therefore we cannot guarantee the blinding of the medical assistants. However, they are not involved in the intervention.
The principal investigator, the GPs and their practices nurses remain blinded during the entire intervention. This is achieved by giving instructions to the patients preferably not to communicate about the intervention with their GPs and practice nurses. To evaluate the success of blinding, GPs will be asked to fill in a questionnaire to investigate to which group each of their participating patients they believed were allocated.
Patients allocated to the control group receive managed diabetes care provided by the DCS.
This managed diabetes care consists of three elements. Firstly, these patients are invited by means of a telephone call from the reception of the DCS to make an appointment for an annual physical examination at the medical assistant. Secondly, the patient visits a diabetes nurse and dietician, for 30 minutes each, in order to receive general information and advice on diabetes problems, dietary intake and physical activity. The results of the physical examination and the recommendations of the diabetes nurses and dietician are sent to the patients' GP, in order to stimulate the GP to follow the guidelines of the Dutch College of General Practitioners [17, 18]. Thirdly, the DCS coordinates the care of the patient between the general practices and secondary diabetes care.
Patients in the control group are scheduled for one visit to the diabetes nurse and for one visit to the dietician; follow-up visits are optional.
Patients who are assigned to the intervention group receive CBT in addition to the same managed care. The CBT is performed by diabetes nurses and dieticians, who received a training of two days in the performing of CBT prior to the onset of the study. Additionally, two instruction days on the implementation of the intervention were arranged. A treatment manual is used during the study to guide the treatment. All CBT sessions are tape-recorded to assess treatment fidelity of the diabetes nurse or dietician to the protocol. In addition, these tape-recordings are used in supervision sessions to provide ongoing feedback. Each diabetes nurse and dietician haves supervision once every four weeks with a psychologist (PvO) who is specialised in CBT. This psychologist is also available by email or telephone between the supervision sessions.
A pilot study was performed before the start of the study to provide three practice sessions for each diabetic nurse and dietician and to assess logistic pathways of the study. There were 10 caregivers involved in the study, which means that 30 patients were included in the pilot study. A supervision meeting was scheduled after the pilot study to discuss logistic pathways and skills to perform the CBT of every caregiver.
The CBT starts with a visit to the diabetes nurse. Results of the baseline measurements can be used to motivate the patient to change. With the help of MI techniques, a problem list is created by the patient focused on lifestyle (smoking behaviour, diet and physical activity). When the most important problem is related to smoking or physical activity, the patient visits the diabetes nurse during the next sessions. When the most important problem is related to diet, the patient is rescheduled to visit the dietician during follow-up sessions. From that moment, the patient remains with the same diabetes nurse or dietician during the entire study.
After the MI phase, is it time to strengthen commitment to a lifestyle change plan. At this point, the patient is willing and able to change. Signs of this readiness for change are: decreased resistance, decreased discussion about the problem, reaching some kind of resolution, increasing change talks, questions about the change, and envisioning how life might be after a change. At this time, the diabetes nurse or dietician makes, together with the patient, an implementation plan where, when and how the behaviour changes will be performed. The formulation of this plan makes it easier for patients to carry out intended actions. This will be done by PST [28–31].
The CBT consists of three to six visits of 30 minutes to the diabetes nurses or dieticians at the DCS. There is a focus on one problem area in each session. During all sessions, both the MI and the PST skills are used to motivate the patients, set new goals and review the patients' progress. The last CBT session is brought to an end by reviewing and emphasising the entire CBT process, with emphasis on achieved successes of the patient and implementation of CBT in the future, independently of the diabetes nurse or dietician. The GPs provide ongoing feedback during the intervention.
Co-interventions and compliance
Co-interventions are avoided during the intervention by means of the fact that the control group was scheduled to a diabetes nurse that did not receive the training on CBT. In addition, all caregivers in the Diabetes Care System have access to the same central database which includes clinical characteristics of the patients and details on given advice and information. This centralisation avoids co-interventions. However, any co-intervention is reported. Compliance to the CBT is assessed by registration of the number of sessions that patients attend.
Compliance to the intervention is considered adequate when at least three sessions are attended. For the patients in the control group, the number of follow-up visits to the diabetes nurse or dietician is also registered. The number of visits to the GPs or hospital is registered for both the intervention and the control group.
Outcome measurements are assessed at baseline, and again after 6 and 12 months by means of self-reported questionnaires and physical examinations at the DCS. Physical examinations are performed by medical assistants of the DCS. These included weight, height, waist circumference, blood pressure, fasting blood glucose, HbA1c, triglycerides (at baseline and 12 months only), total cholesterol (at baseline and 12 months only) and HDL-cholesterol (at baseline and 12 months only). Demographic variables on age, gender, diabetes duration, marital status, ethnicity, level of education and eventual occupation are assessed at baseline by using a self-administered questionnaire, which also includes all secondary outcomes. The medical assistants ask the patients information on medication (the patient brings the packages of medication to the visit), hospital admission days and number of general practitioner visits. Patients are informed of their measurements by the diabetes nurse and dietician. Measurements are also send to their GPs.
Primary outcome measures
The primary outcome measure is the difference between intervention and control group in change in cardiovascular risk score after 12 months. The cardiovascular risk score is based on the Oxford Risk Engine (algorithm that includes: age at diagnosis, duration of diabetes, sex, ethnicity, smoking status, systolic blood pressure, HbA1c, total cholesterol, HDL-cholesterol) .
Secondary outcomes measures
Secondary outcomes measures are included in a self-reported questionnaire that is filled in by the patients at home. Patients will be sent a questionnaire at baseline, after 6 and 12 months. All the secondary outcomes are included in the questionnaire, with the exception of the Patients' evaluation of the Quality of Diabetes Care Questionnaire (PEQD), which is not assessed at baseline.
1. Diet is assessed by the use of the Dutch Eating Behaviour Questionnaire (DEBQ). This is a 33-item questionnaire regarding diet behaviour, scored on a five point scale (1 = never, 2 = seldom, 3 = sometimes, 4 = often, 5 = very often). This questionnaire assess whether a patient is a restraint, emotional or external eater .
2. Short Questionnaire to Assess Health Enhancing Physical Activity (SQUASH) is used to assess physical activity. This questionnaire consists of subscales concerning (A) commuting activities, (B) leisure time activities, (C) household activities, and (D) activities at work and school .
3. Smoking: Smoking is assessed by asking patients if they are a never smoker, current smoker or past smoker.
4. ASE-questionnaire: a 20-item questionnaire, created by the investigators themselves according to the ASE-model: Attitude, Social influences and self-Efficacy model . To our knowledge, no validated questionnaires were available. The theoretical model and questionnaires of other running studies at their own research institute were used to develop the ASE-questionnaire. Each item is provided with a 7-point Likert-type scale describing only the two end points.
5. Quality of life is measured by the EuroQol. This questionnaire consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with 3 levels, and a visual analogue scale on which patients rate their own health between 0 and 100 [42, 43].
6. Depression during the last week is assessed by the use of the CES-D: Center for Epidemiological Studies Depression scale. This is a 20-item questionnaire with a four-point scale (1 = seldom or never, 2 = sometimes, 3 = often, 4 = mostly or always) .
7. The Patient Health Questionnaire (PHQ9) is used to assess the general health of the patient. This brief PHQ consists of 9 items, measured on a four-point scale (1 = not at all, 2 = several days, 3 = more than half of the days, 4 = almost every day) in order to assess depressive disorders during the last two weeks .
8. The patient satisfaction on the diabetes care provided by medical assistants, diabetes nurses and dieticians is measured by the use of the Patients' evaluation of the Quality of Diabetes Care Questionnaire (PEQD). For each health care provider, 14 items are evaluated on a five-point scale, ranging from "poor" to "excellent" .
Physical measurements are performed to calculate the cardiovascular risk score and to describe the patients' characteristics.
1. Anthropometric measurements. Body weight and height are measured for the calculation of the Body Mass Index (weight divided by height squared). Waist circumference is measured at the level midway between the lowest rib margin and the iliac crest.
2. Systolic and diastolic blood pressure is measured after 5 minutes of rest in seated position by Collin Press Mate (BP-8800, Komaki-City).
3. Blood samples are taken in order to determine:
fasting plasma glucose: measured in plasma by means of a hexokinase-method (Roche Diagnostics GmbH, Mannheim, Germany).
HbA1c: measured by High Performance Liquid Chromatography
Total cholesterol, HDL-cholesterol and triglycerides by means of enzymatic techniques (Boehringer-Mannheim, Mannheim, Germany).
4. In addition, data are collected from the patients on:
hospital admission days per 6 months
number of visits to general practitioner per 6 months
medication changes per 6 months
The sample size is calculated on the base of the minimally clinically relevant difference in changes of one of the primary outcome measurements, the Oxford Risk Engine . In the DCS the standard deviation of the absolute risk for cardiovascular disease, calculated with the Oxford Risk Engine, was 10%. A difference (d) between the intervention and control group in changes of 5% absolute risk (about the same as can be expected by giving a cholesterol lowering agent, i.e. a statin as medication), a standard deviation (sd) of 10%, an alpha of 0.05 (two-sided), and a power of 90% leads to 68 participants in each group. A multilevel analysis was performed to calculate the correlation of the outcome measures within practices. A correlation (r) of 20% was found and for that reason the number of participants has to be multiplied with a factor 0.8 (1 – correlation, to adjust for the block randomisation within general practices), leading to 68 patients (n) in each group. The formula used was [47, 48]:
n1 = n2 = 2(Z1-α/2 + Z1-β)2 sd2 (1-r)/d2
Z1-α/2 = Z (1 - 0.05/2) = Z 0.975 = 1.96
Z1-β = Z 0.90 = 1.282
sd = 0.10, r = 0.20, d = 0.05
n1 = n2 = 2 * (1.96 + 1.282)2 * (sd*sd)* (1-r)/(d*d) =
2 * 10.51 * (0.1 * 0.1) * (1 - 0.2)/(0.05 * 0.05) = 68 patients. Taking into account a possible drop-out rate of 30% the number of participants to be randomised must be 194 (97 in each group).
Comparability between the two groups will be assessed at baseline. On the basis of an intention-to-treat analysis, differences in changes between the intervention and the control group are measured with 95% confidence intervals at 12 months for both primary and secondary outcomes. For dichotomous outcome variables a multilevel logistic regression analysis will be used. To calculate differences between continuous variables a multilevel analysis will be used, to adjust for the clustering of observations of patients receiving care from the same GP, and for repeated measurements within one patient. We will also perform a per-protocol analysis with patients that have attended at least three CBT sessions.
We will adjust data for possible confounders: age, gender, weight at start of study, diabetes duration, level of education, depression, smoking, number of attended sessions, general practitioner, and type of health care provider (diabetes nurse or dietician).