Clinical trial NCT04698720: Contribution of Psychological Factors in the Healing of the Diabetic Foot Ulcer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus
Diabetic Foot Ulcer
Keywords: Diabetic Foot Ulcer
Ulcer Healing
Quality of Life
Hypnosis
Relaxation
Lead sponsor: University of Minho
Sponsor class: OTHER
Collaborators: name: Foundation for Science and Technology, Portugal
First posted: 2021-01-07
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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 indicators (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 relaxation and hypnosis interventions, in order to check its effectiveness; as well as the perspectives of informal caregivers on this adjuvant therapys.

Participants must have a diagnosis of Diabetes Mellitus and Diabetic Foot; one or two chronic active ulcers 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 independently with patients that completed the relaxation, hypnosis, and placebo sessions, and with 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 indicators of healing prognosis, and quality of life (QoL), in patients with diabetic foot and a chronic ulcer.

This study will also examine, qualitatively, the perspectives of patients and their respective family caregivers regarding the interventions (EG1 and EG2) and placebo sessions in order to check the treatments' effectiveness.

Specific aim:

1. To compare the impact of both experimental groups (EG1 and EG2) on psychological stress markers, in DFU healing, physiological indicators of 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.

   Nested qualitative study specific aims:
2. To understand the perspectives of patients and family caregivers on the efficacy of EG1 and EG2 interventions versus ACG sessions to the DFU healing, comparing cases with a positive evolution (healing of the DFU) with cases with a negative evolution (DFU non-healing).

Sample size calculation:

Using Sakpal formula (2010), and according to the descriptive results of the pilot study (Ferreira et al., 2022), considering the difference in the mean (1.93) and standard deviation (6) of the treatment versus passive control groups, with a statistical power of 80% and a statistical significance level of 5%, a definitive RCT will require 152 participants. Considering a dropout rate for intervention sessions of 11%, a definitive RCT with four groups will require a sample of 169 participants, with 42 patients per group (Ferreira et al., 2022).

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 an 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. Afterward, 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 confirm the presence of significant clinical levels of stress, anxiety or 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), hypnosis (EG2), or neutral guided imagery (ACG). If allocated to the PCG, the patient will not receive any psychological or placebo session. 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 physiological 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 technicians will not be aware of which group participants belong to.

The interviews with patients who completed the four sessions of EG1, EG2, and ACG, as well as their informal caregivers, will be conducted separately, two weeks after T1, by a different researcher than the one involved in the sessions conduction, to reduce the bias of social desirability.

Data analysis:

All standard statistical analyses will be done using the Rstudio, R version 3.6.2 (R Core Team, 2019) and the SPSS statistics, v. 24.0 (IBM SPSS Statistics for Windows, IBM Corp, Armonk, New York). The baseline data of the treatments and control groups will be compared, using chi-squared test for binary variables and the t-test for continuous variables. The comparison between experimental groups (EG1 and EG2) and control groups (ACG and PCG) will be analyzed through Generalized Mixed Models.

A semi-structured interview guide consisting of open-ended questions will be administered to approximately 12 patients that benefited from interventions (EG1, EG2) and placebo (ACG) sessions), and 12 informal caregivers indicated by those patients. 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, and the NVivo software (QSR International PtyLtd, 2018).

Eligibility criteria: Inclusion Criteria:

* 18 years old or older;
* Diabetes Mellitus diagnosis;
* Diagnosis of Diabetic Foot;
* Having one or two active chronic ulcers (\> 6 weeks and \< 14 weeks) at the time of baseline 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 Multidisciplinary Consultation of the Diabetic Foot of the Hospital de Braga (HB);
* Presenting clinical levels of stress (scores \> 13 for males and \> 17 for females on the Perceived Stress Scale) or anxiety or depression (scores \> 11 on Hospital Anxiety and Depression Scale);
* Providing written informed consent.

Exclusion Criteria:

* The active DFU at the time of the assessment being a relapse;
* Having more than two DFUs at the time of baseline assessment;
* 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 RCT qualitative nested study, twelve participants that completed at least 75% of the treatment or placebo sessions, and that report having a informal/ family caregiver will be invite the participate. Participants will be selected according to the following criteria:

* 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.

Primary outcomes:
measure: Impact of the DFU on patients' quality of life
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Degree of DFU healing
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Physical quality of life
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Mental quality of life
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Metabolic marker
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Inflammatory markers
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Angiogenic markers
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: miRNA markers
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Immune cells
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Secondary outcomes:
measure: Perceived Stress
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Emotional Distress
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Anxiety symptoms
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Depression symptoms
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Representations regarding the DFU
timeFrame: Changes from baseline (T0) to the end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Other outcomes:
measure: Sociodemographic data
timeFrame: Baseline (T0)
measure: Clinical data
timeFrame: Baseline (T0), end of intervention/ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Health literacy
timeFrame: Baseline (T0)
measure: Systolic pressure
timeFrame: Before and after each intervention session at week 2 (1st session), week 4 (2nd session), week 6 (3rd session), and week 8 (4th session). Also, after the baseline (T0), end of interv./ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Diastolic pressure
timeFrame: Before and after each intervention session at week 2 (1st session), week 4 (2nd session), week 6 (3rd session), and week 8 (4th session). Also, after the baseline (T0), end of interv./ 2 months later at post-test (T1), and after 6 months follow-up (T2)
measure: Heart rate
timeFrame: Before and after each intervention session at week 2 (1st session), week 4 (2nd session), week 6 (3rd session), and week 8 (4th session). Also, after the baseline (T0), end of interv./ 2 months later at post-test (T1), and after 6 months follow-up (T2)
Locations:
city: Braga
country: Portugal
facility: Hospital de Braga
city: Penafiel
country: Portugal
facility: Clínica do Pé Diabético, Centro Hospitalar do Tâmega e Sousa
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário do Porto
Study officials:
affiliation: School of Psychology, University of Minho
name: M. Graça Pereira, PhD
role: STUDY_DIRECTOR
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