Contribution of Psychological Factors in the Healing of the Diabetic Foot Ulcer

Contribution of Psychological Factors in the Healing of the Diabetic Foot Ulcer, in Physiological Indicators of Healing Prognosis and Quality of Life: a Randomized Longitudinal Trial With a Nested Qualitative Study of Effectiveness Assessment

Sponsors

Lead Sponsor: University of Minho

Collaborator: Foundation for Science and Technology (Portugal)

Source University of Minho
Brief Summary

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. Research suggests that psychological factors may play an important role in DFU healing. Relaxation and hypnosis seem 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 chronic wounds such as DFU. This study will evaluate the efficacy of relaxation and hypnosis, both with guided imagery, in DFU healing, physiological (inflammatory, metabolic, oxidative stress, angiogenic, and miRNA biomarkers) of wound healing prognosis and QoL, in patients with diabetic foot and a chronic ulcer. This study is a Randomized Controlled Study of a Psychological Intervention that aims to evaluate the efficiency of a muscle relaxation intervention with guided imagery (experimental group - EG1) compare to a hypnosis intervention with guided imagery (experimental group - EG2) and a neutral guided imagery placebo (active control group - ACG) and a group that does not receive any psychological intervention (passive control group - PCG). This study will also examine, qualitatively, the perspectives of patients with DFU on the hypnosis intervention, in order to check its effectiveness; as well as the perspectives of informal caregivers on this adjuvant therapy. 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 four conditions - EG1, EG2, 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 hypnosis sessions and to the informal caregivers 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

General Aim: This RCT aims to assess the effectiveness of a muscle relaxation intervention with guided imagery (EG1) compared to hypnosis with guided imagery intervention (EG2) and a neutral guided imagery placebo (ACG) and a group that does not receive any psychological intervention (PCG), in DFU healing, physiological of wound healing prognosis and Quality of life, in patients with diabetic foot and a chronic ulcer. This study will also examine, qualitatively, the perspectives of patients with DFU regarding the interventions (EG1 and EG2) in order to check its effectiveness; as well as the perspectives of informal caregivers on this adjuvant therapy. Specific aim: 1. To compare the impact of both experimental groups (EG1 and EG2) on psychological stress markers, in DFU healing, physiological indicators (inflammatory, metabolic, oxidative stress, angiogenic, and miRNA biomarkers) healing prognosis and QoL compared to the (PCG); between pre and post intervention in the EG1 and EG2, controlling for clinical and sociodemographic variables, adherence to DFU care and patients' literacy. Qualitative study nested in RCT specific aims: 2. To assess psychological markers (anxiety, depression and stress), physiological indicators of healing prognosis (markers inflammatory diseases, biochemical parameters, angiogenic markers, micro RNAs, and T lymphocyte populations), adherence to UPD care, degree of UPD healing, QOL and family support / care informal, over time in patients with chronic DFU undergoing EG1 versus patients undergoing EG2 versus patients undergoing PCG and versus patients undergoing ACG. 3. To assess the evolution of psychological stress markers, physiological indicators of healing prognosis, adherence to UPD care, QOL and family support / informal care in patients with chronic DFU undergoing EG1, comparing a case with a positive evolution (healing of the DFU) with a case with a negative evolution ( DFU healing). 4. To assess the evolution of psychological stress markers, physiological indicators of healing prognosis, adherence to UPD care, QOL and family support / informal care in patients with chronic DFU undergoing EG2, comparing a case with a positive evolution (healing of the DFU) with a case with a negative evolution ( DFU healing). Sample size calculation: The sample size calculation considering the average effect size of 0.5, a statistical power of 80% and a significance level of 5%, and the number of variables in structural equation models, revealed that 12 participants were needed in each of the groups (12X4), totalizing 48 participants. 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 four 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 (EG1), from four sessions of hypnosis (EG2) or neutral guided imagery (ACG) or a group that does not receive any psychological intervention (PCG). 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. At T0, T1 and T2 a blood and DFU swab sample will be collected for the evaluation of the physiology variables. Plasma and peripheral blood mononuclear cells (PBMC)s will be separated from the blood samples and frozen at -80ºC for analysis by the biochemical team member. Blood lymphocyte populations will be analyzed by flow cytometry and the quantification of blood cell populations will be performed by an automated hematological cell counter on fresh blood samples. The medical and nurse team member as well as the lab techniques will not be aware of which group participants belong to. The interviews with patients, who completed the four sessions of (EG1) and (EG2), and with informal caregivers, 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. Data analysis: All standard statistical analyses will be done using the IBM SPSS statistics 24 and IBM SPSS Amos 24. The comparison between (PCG) and (EG1) and (EG2) and (ACG) over time, will be analyzed through Generalized Mixed Models. A semi-structured interview guide consisting of open-ended questions will be administered to patients with DFU that benefited from interventions (EG1, EG2) and the informal caregivers indicated by the patient that help with 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 anonymized in order to safeguard participants and data confidentiality. The transcripts of the interviews will be analyzed in the same order as conducted, using the thematic content analysis technique.

Overall Status Recruiting
Start Date February 1, 2019
Completion Date July 31, 2022
Primary Completion Date October 1, 2021
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Rate of eligibility Baseline (T0)
Rate of recruitment Baseline (T0)]
Rate of refusal Baseline (T0)]
Rate of adherence to the study protocol Through study completion, an average of 6 months
Rate of participation in follow-up Through study completion, an average of 6 months
Rate of dropout Through study completion, an average of 6 months
Inflammatory markers Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Oxidative Stress marker Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Angiogenic markers Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Metabolic markers Only at baseline (T0)
miRNA markers Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Secondary Outcome
Measure Time Frame
Degree of DFU healing Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Impact of DFU on patients' Quality of Life Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Physical Quality of Life Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Mental Quality of Life Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Perceived Stress Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Emotional Distress Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Anxiety symptoms Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Depression symptoms Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Adherence to DFU Care Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Representations regarding the DFU Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Systolic Pressure Before and after each intervention at 2 weeks (1st Session), 4 weeks (2nd Session), 6 weeks (3rd Session) and 8 weeks (4th Session), after the baseline (T0)
Diastolic Pressure Before and after each intervention at 2 weeks (1st Session), 4 weeks (2nd Session), 6 weeks (3rd Session) and 8 weeks (4th Session), after the baseline (T0)
Heart rate Before and after each intervention at 2 weeks (1st Session), 4 weeks (2nd Session), 6 weeks (3rd Session) and 8 weeks (4th Session), after the baseline (T0)
Enrollment 48
Condition
Intervention

Intervention Type: Behavioral

Intervention Name: Muscle Relaxation with Guided Imagery

Description: 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.

Arm Group Label: Muscle Relaxation with Guided Imagery

Intervention Type: Behavioral

Intervention Name: Hypnosis with Guided Imagery

Description: In the beginning of the first session we apply the Eye-Roll Test for Hypnotizability of Herbert Spiegel. Each session follows the Hypnotic Protocol with the following steps:Pre-talk/Absortion/Ratification/Aliciation/Dissociation/Awakening. The four sessions train the participants in visual, auditory and kinesthetic perception on ulcer healing. The protocol also promotes medical treatment acceptance.

Arm Group Label: Hypnosis with Guided imagery

Intervention Type: Behavioral

Intervention Name: Neutral Guided Imagery

Description: 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.

Arm Group Label: Active Control Group

Eligibility

Criteria:

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 RCT, twelve participants must meet the same inclusion and exclusion criteria defined above, plus being allocated to the EG1 or EG2 or ACG or PCG. From those participants, the following cases will be selected: - Two typical cases of successful and unsuccessful 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; - Two typical cases of successful and unsuccessful 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
M. Graça Pereira, PhD Study Director School of Psychology, University of Minho
Overall Contact

Last Name: M. Graça Pereira, PhD

Phone: 938471039

Phone Ext.: +351

Email: [email protected]

Location
Facility: Status: Contact:
Clínica do Pé Diabético, Centro Hospitalar do Tâmega e Sousa | Penafiel, 4564-007, Portugal Recruiting Maria de Jesus Dantas, MD [email protected]
Centro Hospitalar Universitário do Porto | Porto, 4099-001, Portugal Recruiting André Carvalho, PhD [email protected]
Location Countries

Portugal

Verification Date

January 2021

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University of Minho

Investigator Full Name: Maria da Graça Pereira

Investigator Title: Associate Professor with Aggregation of School of Psychology

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Muscle Relaxation with Guided Imagery

Type: Experimental

Description: 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.

Label: Hypnosis with Guided imagery

Type: Experimental

Description: The participants in Experimental Group will receive a four individual 45-minute sessions, every two weeks, of hypnotic intervention with guided imagery focused on ulcer healing, carried out by the Hypnotherapist on the day of the Diabetic Foot appointments.

Label: Active Control Group

Type: Placebo Comparator

Description: 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.

Label: Passive Control Group

Type: No Intervention

Description: The participants in the Passive Control Group will not receive any intervention nor placebo session.

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: Parallel Assignment This is a Randomized Controlled Study of a Psychological Intervention (Grant et al., 2018). This study will use a mixed-methods approach nested in a 4-arm randomized control design. Qualitative and quantitative data will be collected in order to provide better understanding about the effectiveness of the hypnosis intervention in patients with DFU. Participants will be randomised at a ratio of 1:1 for the four conditions - EG1, EG2, 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, EG2 and ACG; T1), as well as six months later (T2) in a follow-up evaluation. Participants from all four 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).

Primary Purpose: Treatment

Masking: Double (Participant, Outcomes Assessor)

Masking Description: Double (Participant, Outcomes Assessor) Eligible participants will be randomized into the four groups into blocks of variable size, multiples of three; and will be stratified according to: i) data collection site; ii) Chronic Renal Disease; and iii) Peripheral Arterial Disease; because they are factors of poor prognosis in the DFU healing (Ferreira et al., 2014). This procedure will be performed using an online random number generator, by a researcher external to the team involved in the implementation of this study, in order to ensure the concealment of the allocation of participants by the various groups (Pandis, 2012). After this procedure, it will not be possible to conceal the group to which the patient belongs from the researcher who will perform the psychological intervention. However, health professionals (doctors and nurses) will be blinded during the entire procedure, because they fill in the RESVECH 2.0, which assesses the DFU healing.

Source: ClinicalTrials.gov