Study design and participants
This randomized placebo-controlled trial was conducted between September 2019 and January 2020, in the Beheshti hospital (section of Endocrinology) in Kermanshah, Iran. participants include all neuropathic diabetic patients (type 2 diabetes Mellitus) with VD deficiency referred to Beheshti hospital, Kermanshah, Iran, between 1 September 2019 and 18 October 2019. Type 2 diabetes mellitus and neuropathy were diagnosed by a group include endocrinologist and neurologist physicians.
Inclusion and Exclusion criteria
Inclusion criteria include (1) lack of major co-morbid disease such as coronary heart disease or psychotic disorder (2) age of 20 to 70 years, (3) willingness to participate to study and (4) VD insufficiency or deficiency [ between 10 (ng/mL) to 30 (ng/mL) serum vitamin D]. Exclusion criteria include (1) existence of psychiatric or neurological diseases, (2) took VD or any multi-vitamins during the last three months, (3) using any substance and drinking alcohol, (4) pregnancy, and (5) more than one session absent in mindfulness groups.
Randomization and blinding
Participants were randomly allocated into groups using a random table. All patients were blinded to receive VD or placebo groups. Also as these treatments are adjunctive treatments, so, they received usual treatment based on neurologist prescribes.
Concerning 0.2 as type 2 error (with 80%power) and 0.05 as type 1 error; and regarding pervious research, 35 participants are required for each group. toward covering potential dropouts, the sample size increased 25% and reaches to 45 subjects for each group (17).
The patients are randomly allocated into the following groups:
- group 1: mindfulness training
- group 2: mindfulness training + VD supplement
- group 3: mindfulness training + Placebo
- group 4: VD supplement
- group 5: placebo
Between 1, November 2019 to 24, January 2020 (12 weeks), VD groups received a daily four thousand IU oral dosage (four capsules) with 28,000 IU vitamin D weekly. This supplement includes twenty-eight oily drops weekly (JALINOUS CO, Iran). Placebo (JALINOUS) groups receive totally similar drops in shape (without any VD) and duration.
patients allocated to the mindfulness groups received 12 weeks (90 minutes per session) of modified mindfulness manual which based on pain relief protocols(18, 19). the intervention has been implemented by a three trained psychotherapist in mindfulness with three assistances. they were blinded about study aims and the existence of other groups (VDs and other mindfulness groups). For comparing adherence, audios of sessions were recorded with the permission of all the members. Then a mindfulness psychotherapist checked contents secession. Sessions were divided into 15 minutes’ modules that were taken for adherence checks randomly. The treatment position and the occurrence processes were evaluated. Based on the intervention manual, the modules assessed the adherence level as either enough or not sufficient. The majority of content (88%) was judged as implemented adequately.
Session content are including:
- familiarity with participants. Discuss about neuropathy and its nature. giving a pamphlet about neuropathy for home reading. free discussion about the psychological aspect of neuropathy and pain.
- Introduce the content of the intervention. Teaching about the relationship between mind and body.
- learn about meditation and body scan, then practicing them.
- teaching relaxation skills (belly breathing, guided imagery and progressive muscle relaxation).
- Teaching regarding chronic pain, relationships between physical, emotional and thoughts reactions. Also explain pain coping strategies with brain storming.
- Learn to experience negative emotions and pay attention to them.
- Meditation in sitting posture while concentrating on breathing and external sounds.
- Meditation in sitting posture while concentrating on internal emotions and thoughts.
Ten ML of fasting blood units from each participant was taken after ten hours of fasting at the first stage and at the end of the study. The blood samples stored at −80°C (with 10minutes centrifuging at 3000 Revolutions per minute) until future analysis with centrifuged to isolate serums. Fasting blood glucose (FBS) was measured by spectrophotometry utilizing the Pars Azmun kit in auto-analyzer equipment (BT3000, China).
The Pain Disability Index (PDI) is a seven-items scale to examine the extent of self-reported pain-related inability, independent from the region of pain or diagnosis. The items of the scale are evaluated on a 0–10 numeric evaluation scale in which 0 indicates no inability and 10 is the maximum disability. Higher scores indicating higher interference of the pain with regular activities. The PDI showed high test-retest reliability in many studies (20).
Neuropathic pain severity:
The Neuropathic pain scale(NPS) is measured for severity of neuropathic pain. This scale calculated as the sum of ten pain descriptor items (each item rated on 0 to 10 with ten representing the most severe pain). Thus, this scale total score varies from 0 to 100. in many studies, psychometric properties were examined and results showed adequate properties(21).
Neuropathy Specific Quality of Life:
The Neuropathy Specific Quality of Life questionnaire (NeuroQol) with 28 items is a particular validated scale for neuropathic QOL. NeuroQol evaluates diabetic neuropathy-related emotional and physical difficulties affecting diurnal life and well-being. this scale consists of painful symptoms, paresthesia, unsteadiness while walking or standing, emotional distress, interpersonal problems, emotional and physical dependence on others, restriction in daily activities and e.t in five subscales. Higher scores mean more impairments of QOL. Reliability of the subscales ranged from 0.86 to 0.95(22).As four items repeated in more than one subscale, the total score is between 31 to 155.
Sun exposure time:
before implementing intervention and in the post-test by a validated questionnaire the sun exposure rate was assessed. The span of sun exposure was measured by total minutes exposing to the sun in the last two week and divided into two.(23).
Vitamin D intake:
for assessing Vitamin D intake, the fourth version Modified Nutritionist software program was used by a trained nutritionist (three-days food recording include one weekend day and two weekdays.
BMI (Body mass index) by dividing weight (kg) to square height (m2) was calculated. at the baseline and post-test(24).
The short version of the International Physical Activity Questionnaire (SF-IPAQ) was applied for determining the level of physical activity (MET-minutes/week) participants(25).
For assessing data SPSS version 26 was employed and we used paired sample t-test, the one-way ANOVA and, post-hoc test (Scheffe). P-values <0.05 were considered statistically significant.