Relaxation Intervention in Patients With Diabetic Foot Ulcer

Study Overview
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Brief Summary
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Diabetic foot ulcers (DFU) are one of the most serious complications of diabetes and can lead to amputations in 85% of cases, resulting in physical, psychological, family, social and economic consequences. Psychological interventions can contribute to the improvement of wound healing and, relaxation, in particular, seems to contribute to faster wound healing. More research is needed to assess the effectiveness of different types of intervention on different types of wounds, in particular on chronic wounds such as DFU. This is a Pilot Randomised Controlled Study of a Psychological Intervention that aims to evaluate the feasibility and acceptability of a muscle relaxation intervention with guided imagery (experimental group - EG) compared to a neutral guided imagery placebo (active control group - ACG) and a group that does not receive any psychological intervention (passive control group - PCG), to inform a future definitive Randomised Controlled Study (RCT) that tests its effectiveness. This study will also examine, qualitatively, the perspectives of patients with DFU on the relaxation intervention, in order to check its acceptability and applicability; as well as the perspectives of health professionals on this adjuvant therapy, its applicability and integration into the care system of multidisciplinary diabetic foot consultations. Participants have a diagnosis of Diabetes Mellitus and Diabetic Foot; one or two chronic ulcers active at the time of assessment; and clinical levels of stress or anxiety or depression. Participants will be randomized by the three conditions - EG, ACG and PCG - and assessed on the day of the first consultation or nursing treatment for chronic DFU (T0), two months later (T1), and six months later (T2; follow-up). Two weeks after T1, an interview will be conducted with patients with DFU that benefited from the relaxation sessions and to the health professionals who provided them the DFU care. The results of the present study will contribute for a better understanding of DFU progression, healing, prevention of re-ulceration and future amputations and, consequently, for the improvement of patients' quality of life.

Detailed Description
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General Aims: This pilot RCT aims to assess the feasibility and acceptability of a muscle relaxation intervention with guided imagery (experimental group - GE) compared to a neutral guided imagery placebo (active control group - ACG) and a group that does not receive any psychological intervention (passive control group - PCG), prior to the implementation of a future definitive RCT that will assess its effectiveness. This study will also examine, qualitatively, the perspectives of patients with DFU regarding the relaxation intervention, in order to check its acceptability and applicability; as well as the perspectives of health professionals on this adjuvant therapy, its applicability and integration into the multidisciplinary team of diabetic foot consultations. Pilot RCT specific aims: To evaluate the rates of eligibility, recruitment and adherence to the study protocol, participation in follow-up, and withdrawal. The degree of patient satisfaction with the relaxation intervention will also be assessed. To verify the feasibility of the assessment protocol and to obtain preliminary estimates of the effects of the intervention on health outcome measures (degree of DFU healing, DFU-related quality of life, anxiety, depression and stress, DFU representations and physical and mental quality of life); Synthesize the information to estimate the sample size required for a future definitive RCT. Qualitative study nested in Pilot RCT specific aims: To understand the perspective of patients and health professionals about the relaxation sessions; To explore the contribution of the relaxation sessions to the DFU healing and patients' quality of life; To describe the changes perceived in the patient during the period of relaxation sessions; To analyse the relevance of implementing relaxation sessions in the multidisciplinary team consultation of diabetic foot. Data Analysis: To assess the feasibility of this pilot study (aim 1), the rates of eligibility, recruitment and adherence to the study protocol, participation in the follow-up and withdrawal will be calculated and its results will be presented in percentage. The results of the degree of satisfaction with the intervention will be presented through mean and standard deviation. To obtain preliminary estimates of the intervention effects' on health outcome measures (aim 2), descriptive measures of the respective variables (means and standard deviations) will be calculated and Generalised Mixed Models will be used to check for statistically significant differences over time, in the different groups. Data will be analysed using IBM SPSS Statistics 26 for Mac. Finally, from the data obtained, the sample size for a future definitive RCT will be calculated (aim 3). To answer the aims 4 to 7, a semi-structured interview guide consisting of open-ended questions will be administered to patients with DFU that benefited from the relaxation sessions and to the health professionals who provided them the DFU care. This script will remain unchanged throughout the interviews. The audio recording of the interviews will be done using a tablet, transcribed verbatim and anonymised in order to safeguard participants and data confidentiality. The transcripts of the interviews will be analysed in the same order as conducted, using the thematic content analysis technique (Bardin, 2016). Sample size calculation: The sample size calculation for a pilot RCT, considering the average effect size of 0.5, a statistical power of 80% and a significance level of 5%, revealed that 12 participants were needed in each of the groups (Cocks & Torgerson, 2013). This approach considers that a one-sided 80% confidence interval for the effect size will exclude the minimum clinically significant difference if the null hypothesis is true (Brown & Lilford, 2006). Procedure: The doctor or nurse, in the medical appointment, identifies patients that meet the medical inclusion criteria. Patients are invited to participate in the study by the Researcher at the end of the medical appointment and are informed about the aims of the study and the voluntary nature of participation through informed and informative consent. If patients agree to participate, they will sign the consent form. Nurses will then complete RESVECH 2.0 at the end of the appointment and doctors will complete the clinical questionnaire. Afterwards, the Researcher will accompany the patient to a room provided by the Hospital in order to administer the battery of questionnaires in the interview format. After answering the questionnaires, the researcher will score the PSS and HADS instruments to identify the presence of significant clinical levels of stress, anxiety and depression, and if the patient is eligible, at the end of that week, the participant will be randomized into one of three possible groups. In the next diabetic foot appointment, the respective participant will be informed about the group to which he or she has been allocated and whether will benefit, if appropriate, from four sessions of relaxation (EG) or neutral guided imagery (ACG), depending on the group. If the participant is available, the first session will take place on the same day. The following sessions will be scheduled according to the medical diabetic foot consultations. In each session, two assessments of blood pressure and heart rate will be performed, before starting the session and at the end of the session. At the end of the fourth session, the T1 assessment will be performed, with a new administration of the questionnaires. Six months after T0, the T2 (follow-up) evaluation will take place, with the last administration of the questionnaires. The interviews with patients, who completed the four sessions of relaxation, and with health professionals, will be conducted two weeks after T1, by a different researcher than the one involved in the intervention, to reduce the bias of social desirability.

Official Title
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Relaxation Intervention in Patients With Diabetic Foot Ulcer: A Pilot Randomized Controlled Trial With a Nested Qualitative Study

Conditions
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Diabetes Mellitus, Diabetic Foot Ulcer

Intervention / Treatment
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* Behavioral: Muscle Relaxation with Guided Imagery
* Behavioral: Neutral Guided Imagery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetes Mellitus diagnosis; Diagnosis of Diabetic Foot; Having one or two active chronic ulcers (> 6 weeks) at the time of the assessment; Being followed at the Multidisciplinary Consultation of the Diabetic Foot from the Centro Hospitalar Universitário do Porto (CHUP), at the Diabetic Foot Clinic from the Centro Hospitalar do Tâmega e Sousa (CHTS) and from the Hospital de Braga; Presenting clinical levels of stress (scores greater than 13 for males and greater than 17 for females on the Perceived Stress Scale) or anxiety or depression (scores greater than 11 on Hospital Anxiety and Depression Scale). Exclusion Criteria: The active DFU at the time of the assessment being a relapse; Having more than two DFU currently active; Being on hemodialysis treatment; Presence of psychosis or dementia described in the patient's medical record; Having cancer disease; Having undergone a transplant; Receiving psychological counselling at the time of the assessment. For the qualitative study nested in the Pilot RCT, participants must meet the same inclusion and exclusion criteria defined above, plus being allocated to the EG and have completed the four intervention sessions. From those participants, the following cases will be selected: Three typical cases of patients with neuropathic foot defined by the presence of neuropathic pain (e.g., heat, tingling, electrical shock), presence of distal pulses by palpation, and loss of protective sensitivity; Three typical cases of patients with neuroischemic foot defined by the presence of peripheral artery disease, intense-variable pain, absence of distal pulses by palpation, and variable protective sensitivity.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: This is a Pilot Randomised Controlled Study of a Psychological Intervention (Eldridge et al., 2016; Grant et al., 2018). This study will use a mixed-methods approach nested in a pilot 3-arm randomized control design. Qualitative and quantitative data will be collected in order to provide better understanding about the feasibility and acceptability of the relaxation intervention in patients with DFU. Participants will be randomised at a ratio of 1:1 for the three conditions - EG, ACG and PCG; and will be evaluated on the day of the first chronic DFU appointment or nursing treatment (T0), two months later (at the end of the intervention in EG and ACG; T1), as well as six months later (T2) in a follow-up evaluation. Participants from all three groups will undergo standard treatment for the DFU, according to the guidelines of the Portuguese General Health Direction (DGS, 2010) and the International Working Group on the Diabetic Foot (IWGDF, 2015).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Muscle Relaxation with Guided Imagery<br>The participants in Experimental Group will receive four individual 45-minute sessions, every two weeks, of progressive muscle relaxation intervention with guided imagery focused on ulcer healing, carried out by the Psychologist responsible for implementing the project, on the day of the Diabetic Foot appointments. | Behavioral: Muscle Relaxation with Guided Imagery<br>* Relaxation intervention session begins with diaphragmatic breathing, followed by Jacobson's progressive muscle relaxation, which involves the contraction and subsequent relaxation of the 16 muscle groups of the body (forearm, arm, upper forehead, eye, mouth, jaw and throat, neck, shoulder, chest, stomach, thigh, leg and foot). The contraction is performed for 7 seconds while the relaxation lasts for about 40 to 50 seconds. The relaxation of the foot muscle group is only performed on the healthy foot, because dressing and bandages may bandage the foot with the DFU, which together with the typical joint stiffness of the diabetic foot, make it difficult to perform. After muscle relaxation, begins the guided imagery focused on DFU healing. The patient is instructed to think about his/her current state of health and to imagine the DFU as a dark area and the healing relaxation as a light associated to pleasant sensations, which will focus on the foot with DFU to heal it.<br>|
| Placebo Comparator: Active Control Group<br>Participants in the Active Control Group will receive four individual 45-minute sessions of neutral guided imagery placebo, carried out by the Psychologist responsible for implementing the project, on the day of the Diabetic Foot appointments. | Behavioral: Neutral Guided Imagery<br>* This placebo consists on neutral guided imagery focused on themes of the patient's daily life before having DFU. Each session has a theme associated with the patient's life - family, work, friends and leisure. Initially, the patient is asked to think about an event related to the theme of the session of his/her choice, be it positive or negative, which occurred before patient has the current DFU. Then, questions are asked which allow a more detailed reconstruction of the event and the patient is asked to imagine according only to the instructions given. When the whole episode is remembered, the patient is asked to tell what he or she imagined/remembered in each of the questions given.<br>|
| No Intervention: Passive Control Group<br>The participants in the Passive Control Group will not receive any intervention nor placebo session. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of eligibility | This rate will result from the proportion between the number of eligible patients and the total number of observed patients, in percentage. | Baseline (T0) | 
| Rate of recruitment | This rate will result from the proportion between the number of patients who accepted to participate and the number of eligible patients, in percentage. | Baseline (T0) | 
| Rate of refusal | This rate will result from the proportion between the number of patients who rejected to participate in the study and the number of patients invited to participate, in percentage. | Baseline (T0) | 
| Rate of adherence to the study protocol | This rate will result from the proportion between the number of patients who performed the assessments/intervention sessions and the number of patients who completed the baseline assessment (T0), in percentage. | Through study completion, an average of 6 months | 
| Rate of participation in follow-up | This rate will result from the proportion between the number of patients who participated in follow-up assessment and the number of patients who completed the baseline assessment (T0), presented in percentage. | Through study completion, an average of 6 months | 
| Rate of dropout | This rate will result from the proportion between the number of patients who dropout the study and the number of patients who completed the baseline assessment (T0), presented in percentage. | Through study completion, an average of 6 months | 
| Patient satisfaction with the relaxation intervention | The degree of patients´ satisfaction with the relaxation intervention will be assessed through questions developed for this purpose, including the degree of general satisfaction with the sessions; the impact on stress, anxiety and depression, and wound healing after the four sessions; the degree of usefulness for patients with DFU; the desire to participate in future sessions; and the recommendation of the sessions to other patients with DFU. All the questions will be assessed on a Likert scale from 1 (very unsatisfied/ none/ totally disagree) to 5 (very satisfied/ extreme/ totally agree). | End of intervention/ 2 months later at post-test (T1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of DFU healing | The degree of DFU healing will be assessed with the Portuguese version of Resultados esperados de la valoración y evolución de la cicatrización de las heridas crónicas Scale [Expected results of the evaluation and evolution of the healing of chronic wounds Scale - RESVECH 2.0] (Marques, 2015). The scores range from 0 to 35, where zero indicates complete healing. | Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after a six month follow-up (T2) | 
| Impact of DFU on patients' Quality of Life | The Diabetic Foot Ulcer Scale-Short Form (DFS-SF; Bann, Fehnel, & Gagnon, 2003; Research version by Pereira & Ferreira, 2018) will be used to assess patients´ DFU-related Quality of Life. Raw scores are transformed into a scale from 0 to 100. Higher results correspond to better DFU-related quality of life. | Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after a six month follow-up (T2) | 
| Physical Quality of Life | The Short-Form Health Survey (SF-36; Ferreira, 1998; Ferreira, Ferreira, & Pereira, 2012) will be administered to assess patients' physical Health-related Quality of Life. Raw scores are transformed into a scale from 0 to 100. Higher results correspond to better physical quality of life. | Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after a six month follow-up (T2) | 
| Mental Quality of Life | The Short-Form Health Survey (SF-36; Ferreira, 1998; Ferreira, Ferreira, & Pereira, 2012) will be administered to assess patients' mental Health-related Quality of Life. Raw scores are transformed into a scale from 0 to 100. Higher results correspond to better mental quality of life. | Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after a six month follow-up (T2) | 
| Perceived Stress | The overall stress perceived by the patient will be assessed through the Perceived Stress Scale (PSS; Trigo, Canudo, Branco, & Silva, 2010). Scores range between 0 and 40, with higher results indicating higher levels of perceived stress. | Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after a six month follow-up (T2) | 
| Emotional Distress | The emotional distress will be assessed through the total score of the Hospital Anxiety and Depression Scale, comprising both anxiety and depression scales (HADS; Pais-Ribeiro et al., 2007). Scores range between 0 and 42, with higher results indicating higher levels of distress. | Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after a six month follow-up (T2) | 
| Anxiety symptoms | The anxious symptomatology will be assessed through the Hospital Anxiety and Depression Scale (HADS; Pais-Ribeiro et al., 2007). Scores range between 0 and 21, with higher results indicating higher levels of anxiety symptoms. | Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after a six month follow-up (T2) | 
| Depression symptoms | The depressive symptomatology will be assessed through the Hospital Anxiety and Depression Scale (HADS; Pais-Ribeiro et al., 2007). Scores range between 0 and 21, with higher results indicating higher levels of depression symptoms. | Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after a six month follow-up (T2) | 
| Adherence to DFU Care | Patient adherence to DFU care will be assessed through the DFU Care Adherence Questionnaire (Research Version by Pereira, Dantas, Brandão, Santos, Carvalho, & Ferreira, 2018), which was developed for this study, according to the guidelines of the Portuguese General Direction of Health (DGS, 2010) and the International Working Group on the Diabetic Foot (IWGDF, 2015). Higher scores indicate better adherence to DFU care. | Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after a six month follow-up (T2) | 
| Representations regarding the DFU | Patient representations regarding the DFU will be evaluated through the Illness Perception Questionnaire - Brief (IPQ-B; Figueiras et al., 2010). The response scale ranges from 0 to 10. Higher scores indicate more threatening representations regarding DFU. | Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after a six month follow-up (T2) | 
| Systolic Pressure | Systolic pressure in millimeters of mercury (mmHg) will be assessed through a validated and certified blood pressure measuring device. | Before and after each intervention (EG) or placebo (ACG) at 2 weeks (1st Session), 4 weeks (2nd Session), 6 weeks (3rd Session) and 8 weeks (4th Session), after the baseline (T0) | 
| Diastolic Pressure | Diastolic pressure in millimeters of mercury (mmHg) will be assessed through a validated and certified blood pressure measuring device. | Before and after each intervention (EG) or placebo (ACG) at 2 weeks (1st Session), 4 weeks (2nd Session), 6 weeks (3rd Session) and 8 weeks (4th Session), after the baseline (T0) | 
| Heart rate | Heart rate in beats per minute (bpm) will be assessed through a validated and certified blood pressure measuring device. | Before and after each intervention (EG) or placebo (ACG) at 2 weeks (1st Session), 4 weeks (2nd Session), 6 weeks (3rd Session) and 8 weeks (4th Session), after the baseline (T0) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetic Foot Ulcer, Relaxation, Ulcer Healing, Quality of Life, Pilot RCT