Dietary Supplement With Magnesium, Vitamins, Rhodiola and L-theanine Stressed Subjects: Randomized Study Versus Placebo (MAGRITTE)

Stress, Psychological Clinical Trial

— MAGRITTE  

Official title:

Effect of a Dietary Supplement Based on Magnesium, Vitamins, Rhodiola and L-theanine (Stress Resist®), on Stress in Stressed Subjects: Randomized Study Versus Placebo.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04391452
• Other study ID #: RBHP 2019 PICKERING 3
• Secondary ID: 2020-A00040-39
• Status: Completed
• Phase: N/A
• Start date: July 1, 2020
• Est. completion date: July 16, 2021

Study information

• Verified date: April 2020
• Source: University Hospital, Clermont-Ferrand
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim is to study the effect of a dietary supplement on stress and pain through questionnaires and follow-up of physiological parameters, and functional Magnetic Resonance Imaging (fMRI) in stressed healthy subjects versus stressed healthy subjects without treatment.

Description:

The MAGRITTE monocentric study conducted at Clermont-Ferrand University Hospital is a parallel, randomized, and controlled versus placebo performed in stressed subjects.

The main outcome of this study is to demonstrate on stress the effectiveness of a dietary supplement based on magnesium (Mg), vitamins, rhodiola and L-Theanine, compared to placebo, in subjects with chronic stress and free from other pathologies.

The secondary objectives are to evaluate the action of Mg dietary supplement on:

1. pain by the Numerical Scale and fMRI,

2. stress by the Numerical Scale and fMRI,

3. anxiety, depression and sleep with questionnaires,

4. selected biological parameters,

5. heart rate variability,

6. microbiota,

7. safety of the product.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: July 16, 2021
• Est. primary completion date: June 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male or female aged 18 to 65,

• Subject with stress (DASS-42 screening scale =14) and having been under stress for at least 1 month,

• Subject free of any introduction of new treatment or diet at the time inclusion,

• Subject free of any treatment in the 7 days prior to inclusion including no use of analgesic or anti-inflammatory drugs,

• Cooperation and understanding sufficient to comply with the requirements of the study,

• Acceptance to give written consent,

• Affiliation with the French Social Security,

• Registration or acceptance of registration in the national register of volunteers participating in Research.

Exclusion Criteria:

• Contraindications to the realization of MRI without injection such as claustrophobia proven, hearing aid, pacemaker wearers, wearing a brain clip,

• Contraindication to Mg administration: hypersensitivity to Mg oxide, or to one of the excipients,

• With magnesemia > 1.07 mmol/l,

• With moderate (or more severe) kidney failure with creatinine clearance <60 ml/min,

• Receiving a treatment or dietary supplement containing Mg, pre- or probiotics, or herbal extracts (e.g. anti-stress, anti-inflammatory, analgesic) at the time of inclusion,

• Treated with antibiotics in the three months prior to inclusion,

• Having a medical and/or surgical history judged by the investigator or his or her representative that are not compatible with the trial,

• Evolutionary pathology at the time of the inclusion,

• Excessive consumption of alcohol, tobacco (up to 10 cigarettes per day), coffee, tea or drink containing caffeine (equivalent to more than 4 cups per day) or substance abuse,

• Subject who does not meet the selection criteria for their ability to discriminate against sensations resulting from nociceptive stimulation during psychometric tests,

• Subject who does not meet the selection criteria for their ability to discriminate against colours projected during the fMRI exam,

• Subject participating in another clinical trial, or in the exclusion period, or having received a total amount of compensation of more than 4,500 euros over the 12 months prior to the start of the trial,

• Woman of childbearing age not using an effective contraceptive method, pregnant woman or breastfeeding.

Related Conditions & MeSH terms

• Stress, Psychological

Intervention

Dietary Supplement:
• Stress Resist® (oral dietary supplement)
Stress Resist® (dietary supplement) is composed of Mg (150 mg), Vitamin B6 (0.7 mg), Vitamin B9 (100µg), Vitamin B12 (1.25 µg), rhodiola (222mg), and green tea/L-théanine (125 mg). Oral supplementation. All subjects in the MAGRITTE study will receive either a dietary supplement or a placebo for 28 days (morning intake). The effects on stress will be studied both with questionnaires, biological samples (blood, urine and stool), with a Heart Rate Variability test. 40 subjects (20 subjects per group) will have an fMRI exam.

Locations

Country	Name	City	State
France	CHU de Clermont-Ferrand	Clermont-Ferrand

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure of stress with DASS-42	The measure of stress with stress subscale in magnesium and placebo groups will be performed in order to assess the impact of the dietary supplement on this parameter. This subscale consists of 14 questions of self-evaluation, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of stress	Day 0
Primary	Measure of the impact of a dietary supplement (based on Mg, vitamins, rhodiola and L-Theanine) on stress with DASS-42 after 28 days of treatment	The measure of stress with stress subscale in magnesium and placebo groups will be performed in order to assess the impact of the dietary supplement on this parameter. This subscale consists of 14 questions of self-evaluation, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of stress	Day 28
Secondary	Impact of a dietary supplement on pain induced by thermal stimulation observed by fMRI	Pain intensity will be assessed by the numerical pain rating scale (NPRS): the scale ranges from 0 "no pain" to 10 "maximal tolerable pain" following different thermal stimulations (using Pathway Medoc®) applied in fMRI	Day 28
Secondary	Impact of a dietary supplement on pain induced by thermal stimulation observed by fMRI	Pain intensity will be assessed by the numerical pain rating scale (NPRS): the scale ranges from 0 "no pain" to 10 "maximal tolerable pain" following different thermal stimulations (using Pathway Medoc®) applied in fMRI	Day 0
Secondary	Impact of dietary supplement on pain matrix observed by fMRI	Integration will be measured by BOLD signal at the pain matrix (primary and secondary somatosensory cortex, insular cortex, cingulate cortex prefrontal cortex and Basal Ganglia).	Day 0
Secondary	Impact of dietary supplement on pain matrix observed by fMRI	Integration will be measured by BOLD signal at the pain matrix (primary and secondary somatosensory cortex, insular cortex, cingulate cortex prefrontal cortex and Basal Ganglia).	Day 28
Secondary	Evaluation of the analgesic effect of dietary supplement during the period of 28 days of treatment	A daily pain diary will be given to patients for the 28 days of treatment in order to score their average pain during this period. Pain intensity will be assessed by the NPRS obtained from the daily pain diary: the scale ranges from 0 "no pain" to 10 "maximal tolerable pain".	Over the period of treatment : Day 0 to Day 28
Secondary	Impact of dietary supplement on stress by DASS-42 questionnaire	Stress will be measured by DASS-42 questionnaire in dietary supplement and placebo groups. This subscale consists of 14 questions of self-evaluation Depression Anxiety Stress Scale-42, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of stress	Day 0
Secondary	Impact of dietary supplement on stress by DASS-42 questionnaire	Stress will be measured by DASS-42 questionnaire in dietary supplement and placebo groups. This subscale consists of 14 questions of self-evaluation Depression Anxiety Stress Scale-42, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of stress	Day 14
Secondary	Impact of dietary supplement on stress by DASS-42 questionnaire	Stress will be measured by DASS-42 questionnaire in dietary supplement and placebo groups. This subscale consists of 14 questions of self-evaluation Depression Anxiety Stress Scale-42, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of stress	Day 28
Secondary	Impact of dietary supplement on stress by DASS-42 questionnaire	Stress will be measured by DASS-42 questionnaire in dietary supplement and placebo groups. This subscale consists of 14 questions of self-evaluation Depression Anxiety Stress Scale-42, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of stress	Day 56
Secondary	Effect of dietary supplement on increased stress induced by visual stimulation	Stress intensity will be assessed by the numerical stress rating scale: the scale ranges from 0 "no stress" to 10 "maximal stress" following different visual stimulation induced by different colors during the anticipatory phase in fMRI.	Day 0
Secondary	Effect of dietary supplement on increased stress induced by visual stimulation	Stress intensity will be assessed by the numerical stress rating scale: the scale ranges from 0 "no stress" to 10 "maximal stress" following different visual stimulation induced by different colors during the anticipatory phase in fMRI.	Day 28
Secondary	Evaluation of the stress effect of dietary supplement by numerical scale during the period of 28 days of treatment	Stress intensity will be assessed by the numerical stress rating scale: the scale ranges from 0 "no stress" to 10 "maximal stress" during the ratings framing the fMRI exam before and after taking a dietary supplement.	Over the period of treatment: Day 0 to Day 28
Secondary	Evaluation of the stress effect of dietary supplement by numerical scale	Stress intensity will be assessed by the numerical stress rating scale: the scale ranges from 0 "no stress" to 10 "maximal stress" during the ratings framing the fMRI exam before and after taking a dietary supplement.	Day 28
Secondary	Impact of dietary supplement on stress matrix observed by fMRI	Integration difference will be measured by bold signal at the stress matrix level (hippocampus, prefrontal cortex, amygdala and basal ganglia)	Day 0
Secondary	Impact of dietary supplement on stress matrix observed by fMRI	Integration difference will be measured by bold signal at the stress matrix level (hippocampus, prefrontal cortex, amygdala and basal ganglia)	Day 28
Secondary	Evaluation of stress level by daily diary	Stress level will be observed over 28 days of treatment from the daily diary data using a numerical stress scale: scores ranging from 0 "no stress" to 10 "maximal stress".	Day 0
Secondary	Evaluation of stress level by daily diary	Stress level will be observed over 28 days of treatment from the daily diary data using a numerical stress scale: scores ranging from 0 "no stress" to 10 "maximal stress".	Day 28
Secondary	Effect of dietary supplement on anxiety	Anxiety will be measured by DASS-42 questionnaire in dietary supplement and placebo groups. This subscale consists of 14 questions of self-evaluation Depression Anxiety Stress Scale-42, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of anxiety.	day 0
Secondary	Effect of dietary supplement on anxiety	Anxiety will be measured by DASS-42 questionnaire in dietary supplement and placebo groups. This subscale consists of 14 questions of self-evaluation Depression Anxiety Stress Scale-42, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of anxiety.	day 14
Secondary	Effect of dietary supplement on anxiety	Anxiety will be measured by DASS-42 questionnaire in dietary supplement and placebo groups. This subscale consists of 14 questions of self-evaluation Depression Anxiety Stress Scale-42, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of anxiety.	day 28
Secondary	Effect of dietary supplement on anxiety	Anxiety will be measured by DASS-42 questionnaire in dietary supplement and placebo groups. This subscale consists of 14 questions of self-evaluation Depression Anxiety Stress Scale-42, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of anxiety.	day 56
Secondary	Evaluation of the effect of dietary supplement on depression	Depression will be measured by DASS-42 questionnaire in dietary supplement and placebo groups. This subscale consists of 14 questions of self-evaluation Depression Anxiety Stress Scale-42, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of depression	day 0
Secondary	Evaluation of the effect of dietary supplement on depression	Depression will be measured by DASS-42 questionnaire in dietary supplement and placebo groups. This subscale consists of 14 questions of self-evaluation Depression Anxiety Stress Scale-42, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of depression	day 14
Secondary	Evaluation of the effect of dietary supplement on depression	Depression will be measured by DASS-42 questionnaire in dietary supplement and placebo groups. This subscale consists of 14 questions of self-evaluation Depression Anxiety Stress Scale-42, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of depression	day 28
Secondary	Evaluation of the effect of dietary supplement on depression	Depression will be measured by DASS-42 questionnaire in dietary supplement and placebo groups. This subscale consists of 14 questions of self-evaluation Depression Anxiety Stress Scale-42, each of them emphasizing a negative emotional symptom, these feelings of uselessness and hopelessness. Each element is evaluated from zero to three, zero being "not present" and three being "very frequently". It assesses mental health by measuring the severity of depression	day 56
Secondary	Evaluation of the effect of the dietary supplement on quality of sleep	The Pittsburg Sleep Questionnaire Index is a self-questionnaire including 19 items. It was developed to measure the quality of sleep over the month before the patient interview. This questionnaire includes 7 components: subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, hypnotic medication use and daytime dysfunction. In scoring the PSQI, seven component are evaluated from 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality. A score > 5 indicates a sleep disturbance.	day 0
Secondary	Evaluation of the effect of the dietary supplement on quality of sleep	The Pittsburg Sleep Questionnaire Index is a self-questionnaire including 19 items. It was developed to measure the quality of sleep over the month before the patient interview. This questionnaire includes 7 components: subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, hypnotic medication use and daytime dysfunction. In scoring the PSQI, seven component are evaluated from 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality. A score > 5 indicates a sleep disturbance.	day 14
Secondary	Evaluation of the effect of the dietary supplement on quality of sleep	The Pittsburg Sleep Questionnaire Index is a self-questionnaire including 19 items. It was developed to measure the quality of sleep over the month before the patient interview. This questionnaire includes 7 components: subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, hypnotic medication use and daytime dysfunction. In scoring the PSQI, seven component are evaluated from 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality. A score > 5 indicates a sleep disturbance.	day 28
Secondary	Evaluation of the effect of the dietary supplement on quality of sleep	The Pittsburg Sleep Questionnaire Index is a self-questionnaire including 19 items. It was developed to measure the quality of sleep over the month before the patient interview. This questionnaire includes 7 components: subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbance, hypnotic medication use and daytime dysfunction. In scoring the PSQI, seven component are evaluated from 0 (no difficulty) to 3 (severe difficulty). The component scores are summed to produce a global score (range 0 to 21). Higher scores indicate worse sleep quality. A score > 5 indicates a sleep disturbance.	day 56
Secondary	Evaluation of the dietary supplement on catastrophism	Pain Catastrophizing Scale (PCS) is a questionnaire in which the patient is asked to describe the kind of thought and emotions they feel during pain. This questionnaire consists of 13 items describing different thoughts or emotions that may be associated with the pain. The patient will have to indicate how much he has these thoughts or emotions when he feels pain by giving a score between 0 and 4, 0: not at all, 4: all the time. The final score is the sum of the scores for each question.	day 0
Secondary	Evaluation of the dietary supplement on catastrophism	Pain Catastrophizing Scale (PCS) is a questionnaire in which the patient is asked to describe the kind of thought and emotions they feel during pain. This questionnaire consists of 13 items describing different thoughts or emotions that may be associated with the pain. The patient will have to indicate how much he has these thoughts or emotions when he feels pain by giving a score between 0 and 4, 0: not at all, 4: all the time. The final score is the sum of the scores for each question.	day 14
Secondary	Evaluation of the dietary supplement on catastrophism	Pain Catastrophizing Scale (PCS) is a questionnaire in which the patient is asked to describe the kind of thought and emotions they feel during pain. This questionnaire consists of 13 items describing different thoughts or emotions that may be associated with the pain. The patient will have to indicate how much he has these thoughts or emotions when he feels pain by giving a score between 0 and 4, 0: not at all, 4: all the time. The final score is the sum of the scores for each question.	day 28
Secondary	Evaluation of the dietary supplement on catastrophism	Pain Catastrophizing Scale (PCS) is a questionnaire in which the patient is asked to describe the kind of thought and emotions they feel during pain. This questionnaire consists of 13 items describing different thoughts or emotions that may be associated with the pain. The patient will have to indicate how much he has these thoughts or emotions when he feels pain by giving a score between 0 and 4, 0: not at all, 4: all the time. The final score is the sum of the scores for each question.	day 56
Secondary	Evaluation of blood Magnesium (Mg) level	The intracellular magnesium concentrations will be determined by the blood samples taken	day 0
Secondary	Evaluation of blood Magnesium (Mg) level	The intracellular magnesium concentrations will be determined by the blood samples taken	day 14
Secondary	Evaluation of blood Magnesium (Mg) level	The intracellular magnesium concentrations will be determined by the blood samples taken	day 28
Secondary	Evaluation of blood Magnesium (Mg) level	The intracellular magnesium concentrations will be determined by the blood samples taken	day 56
Secondary	Evaluation of erythrocyte Mg level	The erythrocyte magnesium concentrations will be determined by the blood samples taken	day 0
Secondary	Evaluation of erythrocyte Mg level	The erythrocyte magnesium concentrations will be determined by the blood samples taken	day 14
Secondary	Evaluation of erythrocyte Mg level	The erythrocyte magnesium concentrations will be determined by the blood samples taken	day 28
Secondary	Evaluation of erythrocyte Mg level	The erythrocyte magnesium concentrations will be determined by the blood samples taken	day 56
Secondary	Evaluation of urinary Mg level	The urinary concentration of magnesium will be determined by the urine collected for 24 hours.	day 0
Secondary	Evaluation of urinary Mg level	The urinary concentration of magnesium will be determined by the urine collected for 24 hours.	day 14
Secondary	Evaluation of urinary Mg level	The urinary concentration of magnesium will be determined by the urine collected for 24 hours.	day 28
Secondary	Evaluation of urinary Mg level	The urinary concentration of magnesium will be determined by the urine collected for 24 hours.	day 56
Secondary	Evaluation of salivary cortisol level	The concentration of cortisol will be determined by salivary cortisol dosage and will be performed before and after fMRI exam.	day 0
Secondary	Evaluation of salivary cortisol level	The concentration of cortisol will be determined by salivary cortisol dosage and will be performed before and after fMRI exam.	day 28
Secondary	Evaluation of Heart Rate Variability	Heart rate variability (HRV / HRV) is a measure of changes in heart rate that will provide an estimate of stress. It is usually calculated by analyzing time series of beat-by-beat intervals of the electrocardiogram or blood pressure plots (using Codesna®).	day 0
Secondary	Evaluation of Heart Rate Variability	Heart rate variability (HRV / HRV) is a measure of changes in heart rate that will provide an estimate of stress. It is usually calculated by analyzing time series of beat-by-beat intervals of the electrocardiogram or blood pressure plots (using Codesna®).	day 14
Secondary	Evaluation of Heart Rate Variability	Heart rate variability (HRV / HRV) is a measure of changes in heart rate that will provide an estimate of stress. It is usually calculated by analyzing time series of beat-by-beat intervals of the electrocardiogram or blood pressure plots (using Codesna®).	day 28
Secondary	Analysis of the microbiota (stool samples)	The stool samples will assess to identify the bacterial biodiversity by a genetic sequencing analysis of bacterial DNA.	day 0
Secondary	Analysis of the microbiota (stool samples)	The stool samples will assess to identify the bacterial biodiversity by a genetic sequencing analysis of bacterial DNA.	day 28
Secondary	Assessment of the occurrence of adverse event	The adverse event will be reported by the patient on his daily diary during the period of treatment, over 28 days.	day 28
Secondary	Assessment of analgesic consumption	Analgesic consumption will be assessed by the daily diary during the period of treatment, over 28 days	Day 28
Secondary	Influence on microbiota assessed by a food survey	A food survey will be performed by the daily diary during the period of treatment, over 28 days. Participant will have to report in his daily diary what he will have eaten per day (breakfast, lunch and dinner).	Day 28