Clinical trial NCT04391452: Dietary Supplement With Magnesium, Vitamins, Rhodiola and L-theanine Stressed Subjects: Randomized Study Versus Placebo (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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stress, Psychological
Keywords: Stressed individuals
Dietary supplement
Magnesium
fMRI
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2020-05-18
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: After pre-selection (Day-14 to Day 0), participants will receive one of the two products in random order (Mg or placebo).

Treatment allocation will follow a randomization plan and will be carried out by a Clinical Research Associate totally independent from the protocol. The randomization list and a copy will be edited, placed in a sealed envelope, and submitted to the Pharmacy of the University Hospital of Clermont-Ferrand and the Clinical Pharmacology Centre of Clermont-Ferrand which is the coordinating centre.

For a 5% risk of bilateral species error and a 90% power, it is necessary to include 50 subjects per group to highlight such an effect size. In addition, fMRI examinations will be offered to the first 20 subjects included per group, i.e. 40 subjects, an usual and relatively consensual number for fMRI work.
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Measure of stress with DASS-42
timeFrame: Day 0
measure: 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
timeFrame: Day 28
Secondary outcomes:
measure: Impact of a dietary supplement on pain induced by thermal stimulation observed by fMRI
timeFrame: Day 28
measure: Impact of a dietary supplement on pain induced by thermal stimulation observed by fMRI
timeFrame: Day 0
measure: Impact of dietary supplement on pain matrix observed by fMRI
timeFrame: Day 0
measure: Impact of dietary supplement on pain matrix observed by fMRI
timeFrame: Day 28
measure: Evaluation of the analgesic effect of dietary supplement during the period of 28 days of treatment
timeFrame: Over the period of treatment : Day 0 to Day 28
measure: Impact of dietary supplement on stress by DASS-42 questionnaire
timeFrame: Day 0
measure: Impact of dietary supplement on stress by DASS-42 questionnaire
timeFrame: Day 14
measure: Impact of dietary supplement on stress by DASS-42 questionnaire
timeFrame: Day 28
measure: Impact of dietary supplement on stress by DASS-42 questionnaire
timeFrame: Day 56
measure: Effect of dietary supplement on increased stress induced by visual stimulation
timeFrame: Day 0
measure: Effect of dietary supplement on increased stress induced by visual stimulation
timeFrame: Day 28
measure: Evaluation of the stress effect of dietary supplement by numerical scale during the period of 28 days of treatment
timeFrame: Over the period of treatment: Day 0 to Day 28
measure: Evaluation of the stress effect of dietary supplement by numerical scale
timeFrame: Day 28
measure: Impact of dietary supplement on stress matrix observed by fMRI
timeFrame: Day 0
measure: Impact of dietary supplement on stress matrix observed by fMRI
timeFrame: Day 28
measure: Evaluation of stress level by daily diary
timeFrame: Day 0
measure: Evaluation of stress level by daily diary
timeFrame: Day 28
measure: Effect of dietary supplement on anxiety
timeFrame: day 0
measure: Effect of dietary supplement on anxiety
timeFrame: day 14
measure: Effect of dietary supplement on anxiety
timeFrame: day 28
measure: Effect of dietary supplement on anxiety
timeFrame: day 56
measure: Evaluation of the effect of dietary supplement on depression
timeFrame: day 0
measure: Evaluation of the effect of dietary supplement on depression
timeFrame: day 14
measure: Evaluation of the effect of dietary supplement on depression
timeFrame: day 28
measure: Evaluation of the effect of dietary supplement on depression
timeFrame: day 56
measure: Evaluation of the effect of the dietary supplement on quality of sleep
timeFrame: day 0
measure: Evaluation of the effect of the dietary supplement on quality of sleep
timeFrame: day 14
measure: Evaluation of the effect of the dietary supplement on quality of sleep
timeFrame: day 28
measure: Evaluation of the effect of the dietary supplement on quality of sleep
timeFrame: day 56
measure: Evaluation of the dietary supplement on catastrophism
timeFrame: day 0
measure: Evaluation of the dietary supplement on catastrophism
timeFrame: day 14
measure: Evaluation of the dietary supplement on catastrophism
timeFrame: day 28
measure: Evaluation of the dietary supplement on catastrophism
timeFrame: day 56
measure: Evaluation of blood Magnesium (Mg) level
timeFrame: day 0
measure: Evaluation of blood Magnesium (Mg) level
timeFrame: day 14
measure: Evaluation of blood Magnesium (Mg) level
timeFrame: day 28
measure: Evaluation of blood Magnesium (Mg) level
timeFrame: day 56
measure: Evaluation of erythrocyte Mg level
timeFrame: day 0
measure: Evaluation of erythrocyte Mg level
timeFrame: day 14
measure: Evaluation of erythrocyte Mg level
timeFrame: day 28
measure: Evaluation of erythrocyte Mg level
timeFrame: day 56
measure: Evaluation of urinary Mg level
timeFrame: day 0
measure: Evaluation of urinary Mg level
timeFrame: day 14
measure: Evaluation of urinary Mg level
timeFrame: day 28
measure: Evaluation of urinary Mg level
timeFrame: day 56
measure: Evaluation of salivary cortisol level
timeFrame: day 0
measure: Evaluation of salivary cortisol level
timeFrame: day 28
measure: Evaluation of Heart Rate Variability
timeFrame: day 0
measure: Evaluation of Heart Rate Variability
timeFrame: day 14
measure: Evaluation of Heart Rate Variability
timeFrame: day 28
measure: Analysis of the microbiota (stool samples)
timeFrame: day 0
measure: Analysis of the microbiota (stool samples)
timeFrame: day 28
measure: Assessment of the occurrence of adverse event
timeFrame: day 28
measure: Assessment of analgesic consumption
timeFrame: Day 28
measure: Influence on microbiota assessed by a food survey
timeFrame: Day 28
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Gisèle Pickering
role: PRINCIPAL_INVESTIGATOR
References: