Treatment Adherence Intervention in Patients With Type 2 Diabetes and Comorbid Depression

Study Overview
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Brief Summary
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Patients with diabetes have higher depression rates, impaired QOL and increased mortality rates due to complications and comorbid depression. Nurse-led, telephonic-based, and psychoeducational interventions have separately proved to improve disease prognosis and emotional distress in diabetes, but no study has integrated previous research findings with collaborative care and strong methods centred in treatment adherence outcomes. The Telephonic Monitoring on Diabetes and co-morbid Depression (TELE-DD) Project includes a three-phased population-based cohort study and nurse-led randomised controlled trial. The proposed intervention, based on monthly structured telephone calls, unifies proved techniques like motivational interviewing, cognitive behavioural therapy and patient's healthy behaviours education. The integration in the TELE-DD Project of previous clinical research and a robust epidemiological dual design, will improve treatment adherence and further prognosis in patients with type 2 diabetes and comorbid depression through maximising clinical outcomes improvement, while guaranteeing cost-effectiveness and the long-term sustainability of findings translation to PC clinical practice services and public health programs.

Detailed Description
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Patients with diabetes mellitus have a depression rate 1.6-2 times higher, impaired quality of life and increased mortality rates due to complications, comorbid depression or both. Prognosis in diabetes and depression comorbidity can be improved by increasing treatment adherence. Nurse-led, telephonic-based, and psychoeducational interventions, centred on motivational interviewing and cognitive behavioural therapy for adherence and depression, have separately improved prognosis and emotional distress in diabetic patients with comorbid depression. The Telephonic Monitoring on Diabetes and co-morbid Depression (TELE-DD) Project aims to integrate prior well-stablished clinical research with collaborative care. A whole population cohort of adults (21+) with type 2 diabetes (T2D) and comorbid depression from twenty-three Health Centres from a whole Health System Region in Spain, will be approached for inclusion in the TELE-DD Project (N=7,271). Patients with confirmed diagnoses and pharmacological treatment for both diseases will be included in Phase I baseline cohort. In Phase II, 400 participants diagnosed with depression and T2D with no treatment adherence will be selected to participate in the randomised controlled trial (RCT). The TELE-DD Project is a three-stage both observational and comparative effectiveness study that includes a population-based cohort study (Phases I and III), and a nurse-led randomised controlled trial (Phase II), aimed to compare a telephonic-based psychoeducational intervention (TIG) vs treatment as usual (TAU) to improve treatment adherence (TA), and a further two- to five-year prognosis and cost-effectiveness study, in T2D patients with comorbid clinical depression from Primary Care (PC) services. The integration in the TELE-DD Project of previous clinical research and a robust epidemiological design, will improve treatment adherence and further prognosis in these through maximising clinical outcomes improvement, while guaranteeing cost-effectiveness and the long-term sustainability of findings translation to PC clinical practice services and public health programs.

Official Title
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The TELE-DD Project: a Nurse-led Randomised Controlled Trial on Treatment Adherence in Patients With Type 2 Diabetes and Comorbid Depression

Conditions
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Diabetes Mellitus, Type 2, Depression

Intervention / Treatment
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* Behavioral: Telephone Intervention Group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult individuals (21+). Concurrent type 2 diabetes (T2D) and depression diagnose registered in the SALUD clinical computerised system before January 1st, 2016. A duration of both T2D and depression of at least one year. Willingness to follow the TELE-DD research nurse instructions including self-monitoring of blood glucose. Fluent in the Spanish language Provision of signed and dated informed consent prior to any study procedures. No treatment adherence to both T2D and depression, or treatment adherence to both. Exclusion Criteria: Presence of hearing problems, Alzheimer Disease, dementia or another serious cognitive or psychiatric disorder. Use of private health insurance that may influence the RCT intervention outcomes. Absence of pharmacological treatment for T2D or depression according to the CHS-EMR. Change of address or place of residence out of SALUD Zaragoza Region II, or no access to a phone. No Primary Care Specialist (PCS) or inability to identify a reference one. Treatment adherence only for one of the two conditions (D2T or depression).

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telephone Intervention Group<br>Nurse-led, telephone-based, and psychoeducational intervention, centered on motivational interviewing and cognitive behavioural therapy for adherence and depression. | Behavioral: Telephone Intervention Group<br>* Nurse-led, telephone-based, and psychoeducational intervention centered on motivational interviewing and cognitive behavioral therapy for adherence and depression.<br>|
| No Intervention: Control group<br>Control group with treatment as usual (TAU). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diabetes control measured by Glycosylated Haemoglobin | In the Intervention and control group | Baseline | 
| Diabetes control measured by Glycosylated Haemoglobin | In the Intervention and control group | 6-month follow-up | 
| Diabetes control measured by Glycosylated Haemoglobin | In the Intervention and Control group | 12-month follow-up | 
| Diabetes control measured by Glycosylated Haemoglobin | In the Intervention and Control group | 18-month follow-up | 
| Patient Health Questionnaire (PHQ-9) | In the Intervention and Control group. The Patient Health Questionnaire (PHQ-9) is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. PHQ scores ≥ 10 had a sensitivity of 88% and a specificity of 88% for major depression. PHQ-9 scores of 5, 10, 15, and 20 represents mild, moderate, moderately severe and severe depression. The possible range is 0-27. | Baseline | 
| Patient Health Questionnaire (PHQ-9) | In the Intervention and Control group. The Patient Health Questionnaire (PHQ-9) is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. PHQ scores ≥ 10 had a sensitivity of 88% and a specificity of 88% for major depression. PHQ-9 scores of 5, 10, 15, and 20 represents mild, moderate, moderately severe and severe depression. The possible range is 0-27. | 6-month follow-up | 
| Patient Health Questionnaire (PHQ-9) | In the Intervention and Control group. The Patient Health Questionnaire (PHQ-9) is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. PHQ scores ≥ 10 had a sensitivity of 88% and a specificity of 88% for major depression. PHQ-9 scores of 5, 10, 15, and 20 represents mild, moderate, moderately severe and severe depression. The possible range is 0-27. | 12-month follow-up | 
| Patient Health Questionnaire (PHQ-9) | In the Intervention and Control group. The Patient Health Questionnaire (PHQ-9) is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression. PHQ scores ≥ 10 had a sensitivity of 88% and a specificity of 88% for major depression. PHQ-9 scores of 5, 10, 15, and 20 represents mild, moderate, moderately severe and severe depression. The possible range is 0-27. | 18-month follow-up | 
| Medication possession ratio (MPR) | In the Intervention and Control group. Medication adherence was assessed using the medication possession ratio (MPR). It is calculated as the proportion of the number of days with treatment provided during the intended period of treatment, that is, 100 × (days supplied) / 365. Once TA is computed, a dichotomous variable is created as TA (Yes/No) considering a cut-off ratio of MPR ≥80%. | Baseline | 
| Medication possession ratio (MPR) | In the Intervention and Control group. Medication adherence was assessed using the medication possession ratio (MPR). It is calculated as the proportion of the number of days with treatment provided during the intended period of treatment, that is, 100 × (days supplied) / 365. Once TA is computed, a dichotomous variable is created as TA (Yes/No) considering a cut-off ratio of MPR ≥80%. | 6-month follow-up | 
| Medication possession ratio (MPR) | In the Intervention and Control group. Medication adherence was assessed using the medication possession ratio (MPR). It is calculated as the proportion of the number of days with treatment provided during the intended period of treatment, that is, 100 × (days supplied) / 365. Once TA is computed, a dichotomous variable is created as TA (Yes/No) considering a cut-off ratio of MPR ≥80%. | 12-month follow-up | 
| Medication possession ratio (MPR) | In the Intervention and Control group. Medication adherence was assessed using the medication possession ratio (MPR). It is calculated as the proportion of the number of days with treatment provided during the intended period of treatment, that is, 100 × (days supplied) / 365. Once TA is computed, a dichotomous variable is created as TA (Yes/No) considering a cut-off ratio of MPR ≥80%. | 18-month follow-up | 
| MBG questionnaire | In the Intervention and Control group. The MBG questionnaire includes TA questions related to timely drug intake, diet, PCS visits, physical activity, self-management, and others; prior research showed a Cronbach's alpha of 69% and a total explained variance of 63%. | Baseline | 
| MBG questionnaire | In the Intervention and Control group. The MBG questionnaire includes TA questions related to timely drug intake, diet, PCS visits, physical activity, self-management, and others; prior research showed a Cronbach's alpha of 69% and a total explained variance of 63%. | 6-month follow-up | 
| MBG questionnaire | In the Intervention and Control group. The MBG questionnaire includes TA questions related to timely drug intake, diet, PCS visits, physical activity, self-management, and others; prior research showed a Cronbach's alpha of 69% and a total explained variance of 63%. | 12-month follow-up | 
| MBG questionnaire | In the Intervention and Control group. The MBG questionnaire includes TA questions related to timely drug intake, diet, PCS visits, physical activity, self-management, and others; prior research showed a Cronbach's alpha of 69% and a total explained variance of 63%. | 18-month follow-up | 
| LDL-Cholesterol | In the Intervention and Control group. LDL-C values were registered according to reference values and recommendations from the National Cholesterol Education Program Adult Treatment Panel III (2001): <100 mg/dl optimum, 100-129 mg normal or close to optimal level, 130-159 mg/dl normal-high, 160-189 mg/dl high,> 190 mg/dl very high. | Baseline | 
| LDL-Cholesterol | In the Intervention and Control group. LDL-C values were registered according to reference values and recommendations from the National Cholesterol Education Program Adult Treatment Panel III (2001): <100 mg/dl optimum, 100-129 mg normal or close to optimal level, 130-159 mg/dl normal-high, 160-189 mg/dl high,> 190 mg/dl very high. | 6-month follow-up | 
| LDL-Cholesterol | In the Intervention and Control group. LDL-C values were registered according to reference values and recommendations from the National Cholesterol Education Program Adult Treatment Panel III (2001): <100 mg/dl optimum, 100-129 mg normal or close to optimal level, 130-159 mg/dl normal-high, 160-189 mg/dl high,> 190 mg/dl very high. | 12-month follow-up | 
| LDL-Cholesterol | In the Intervention and Control group. LDL-C values were registered according to reference values and recommendations from the National Cholesterol Education Program Adult Treatment Panel III (2001): <100 mg/dl optimum, 100-129 mg normal or close to optimal level, 130-159 mg/dl normal-high, 160-189 mg/dl high,> 190 mg/dl very high. | 18-month follow-up | 
| Diabetes Distress Scale (DDS) | In the Intervention and Control group. Four main domains can be identified in DDS: emotional burden, physician-related distress, regimen-related distress, and interpersonal distress, as well as obtaining a total score. Previous analyses identified that DDS had good sensitivity (95%) and specificity (85%), and was considered a reliable (α = 0.93) instrument for clinical practice and research (Polonsky et al., 2005), and has been validated in Spanish language (Ortiz et al., 2013). | Baseline | 
| Diabetes Distress Scale (DDS) | In the Intervention and Control group. Four main domains can be identified in DDS: emotional burden, physician-related distress, regimen-related distress, and interpersonal distress, as well as obtaining a total score. Previous analyses identified that DDS had good sensitivity (95%) and specificity (85%), and was considered a reliable (α = 0.93) instrument for clinical practice and research (Polonsky et al., 2005), and has been validated in Spanish language (Ortiz et al., 2013). | 6-month follow-up | 
| Diabetes Distress Scale (DDS) | In the Intervention and Control group. Four main domains can be identified in DDS: emotional burden, physician-related distress, regimen-related distress, and interpersonal distress, as well as obtaining a total score. Previous analyses identified that DDS had good sensitivity (95%) and specificity (85%), and was considered a reliable (α = 0.93) instrument for clinical practice and research (Polonsky et al., 2005), and has been validated in Spanish language (Ortiz et al., 2013). | 12-month follow-up | 
| Diabetes Distress Scale (DDS) | In the Intervention and Control group. Four main domains can be identified in DDS: emotional burden, physician-related distress, regimen-related distress, and interpersonal distress, as well as obtaining a total score. Previous analyses identified that DDS had good sensitivity (95%) and specificity (85%), and was considered a reliable (α = 0.93) instrument for clinical practice and research (Polonsky et al., 2005), and has been validated in Spanish language (Ortiz et al., 2013). | 18-month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sociodemographic data Gender, age, marital status, education, occupation, economical level | In the Intervention group and the Control group | Baseline | 
| Blood pressure | Blood pressure was measured according to the Spanish Heart Society (Moliner de la Puente et al., 2008), which is based on the National Institute for Health and Clinical Excellence guidelines (NICE, 2011). | Baseline | 
| Blood pressure | Blood pressure was measured according to the Spanish Heart Society (Moliner de la Puente et al., 2008), which is based on the National Institute for Health and Clinical Excellence guidelines (NICE, 2011). | 6-month follow-up | 
| Blood pressure | Blood pressure was measured according to the Spanish Heart Society (Moliner de la Puente et al., 2008), which is based on the National Institute for Health and Clinical Excellence guidelines (NICE, 2011). | 12-month follow-up | 
| Blood pressure | Blood pressure was measured according to the Spanish Heart Society (Moliner de la Puente et al., 2008), which is based on the National Institute for Health and Clinical Excellence guidelines (NICE, 2011). | 18-month follow-up | 
| Body mass index (BMI) | Body mass index (BMI) calculated as weight in kilograms divided by height height in square meters. In patients who are overweight or obese, a moderate reduction in body weight (5-10% of weight) is associated with improved insulin sensitivity, better glycemic control, reduced triglycerides and increased serum c-HDL. | Baseline | 
| Body mass index (BMI) | Body mass index (BMI) calculated as weight in kilograms divided by height height in square meters. In patients who are overweight or obese, a moderate reduction in body weight (5-10% of weight) is associated with improved insulin sensitivity, better glycemic control, reduced triglycerides and increased serum c-HDL. | 6-month follow-up | 
| Body mass index (BMI) | Body mass index (BMI) calculated as weight in kilograms divided by height height in square meters. In patients who are overweight or obese, a moderate reduction in body weight (5-10% of weight) is associated with improved insulin sensitivity, better glycemic control, reduced triglycerides and increased serum c-HDL. | 12-month follow-up | 
| Body mass index (BMI) | Body mass index (BMI) calculated as weight in kilograms divided by height height in square meters. In patients who are overweight or obese, a moderate reduction in body weight (5-10% of weight) is associated with improved insulin sensitivity, better glycemic control, reduced triglycerides and increased serum c-HDL. | 18-month follow-up | 
| Research nurse qualitative and quantitative evaluation about Treatment Adherence and diseases management. | The research nurse will record her qualitative and quantitative evaluation on how she thinks the patient is responding to treatment adherence and any detail of both diabetes and depression management. This evaluation will include a quantitative measure containing a 1-5 scale and a qualitative recording. This assessment will serve as a reference to compare with the patients' responses. | Baseline | 
| Research nurse qualitative and quantitative evaluation about Treatment Adherence and diseases management. | The research nurse will record her qualitative and quantitative evaluation on how she thinks the patient is responding to treatment adherence and any detail of both diabetes and depression management. This evaluation will include a quantitative measure containing a 1-5 scale and a qualitative recording. This assessment will serve as a reference to compare with the patients' responses. | 6-month follow-up | 
| Research nurse qualitative and quantitative evaluation about Treatment Adherence and diseases management. | The research nurse will record her qualitative and quantitative evaluation on how she thinks the patient is responding to treatment adherence and any detail of both diabetes and depression management. This evaluation will include a quantitative measure containing a 1-5 scale and a qualitative recording. This assessment will serve as a reference to compare with the patients' responses. | 12-month follow-up | 
| Research nurse qualitative and quantitative evaluation about Treatment Adherence and diseases management. | The research nurse will record her qualitative and quantitative evaluation on how she thinks the patient is responding to treatment adherence and any detail of both diabetes and depression management. This evaluation will include a quantitative measure containing a 1-5 scale and a qualitative recording. This assessment will serve as a reference to compare with the patients' responses. | 18-month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Comorbidity, Depression, Type 2 Diabetes, Primary Health Care, Randomized-Controlled Trial, Treatment Adherence, Telephone-Based Intervention