Dose-response Relationship of Mustard Flour Footbaths in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
A study to explore whether different dosages of mustard flour in footbaths cause different effects on warmth development as well as on general well-being and the autonomic nervous system.

Detailed Description
-----------------
This is a blinded, four-arm randomized controlled trial with crossover design to explore the dose-response relationship of footbaths with different dosages of mustard flour in healthy volunteers, compared to a placebo control (footbath with warm water only). The main focus is on thermogenesis and warmth distribution, as assessed by high-resolution infrared thermography and questionnaire data before, during and after the intervention. In addition, effects on the autonomic nervous system are assessed by measuring various parameters of heart rate variability and pulse wave analysis.

Official Title
-----------------
Dose-response Relationship of Mustard Flour Footbaths in Healthy Volunteers - a Blinded, Randomized, Controlled, Four-Arm Study With Crossover Design

Conditions
-----------------
Thermogenesis by Different-dosage Mustard Flour Footbaths

Intervention / Treatment
-----------------
* Other: 3-g mustard footbath
* Other: 6-g mustard footbath
* Other: 12-g mustard footbath
* Other: Warm water only


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent; Age between 18 and 55 years Exclusion Criteria: Chronic skin lesions at the lower legs or feet Varicose veins grade 3 and grade 4 (Marshall stage classification) Chronic venous insufficiency Known intolerance or hypersensitivity to mustard preparations Cardiac arrhythmia Cardiac pacemaker Asthma bronchiale Consumption of HRV-modulating medication (especially tricyclic antidepressants, beta blockers) Pregnancy Insufficient knowledge of the german language

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3-g footbath<br>Footbath with 3g mustard flour per liter of water | Other: 3-g mustard footbath<br>* A ten-minute pre-intervention rest period followed by a 20-minute footbath with 12 l of warm water (40 °C) and 36 g mustard flour (3 g per l), followed by a ten-minute post-intervention rest period.<br>|
| Experimental: 6-g footbath<br>Footbath with 6g mustard flour per liter of water | Other: 6-g mustard footbath<br>* A ten-minute pre-intervention rest period followed by a 20-minute footbath with 12 l of warm water (40 °C) and 72 g mustard flour (6 g per l), followed by a ten-minute post-intervention rest period.<br>|
| Experimental: 12-g footbath<br>Footbath with 12g mustard flour per liter of water | Other: 12-g mustard footbath<br>* A ten-minute pre-intervention rest period followed by a 20-minute footbath with 12 l of warm water (40 °C) and 144 g mustard flour (12 g per l), followed by a ten-minute post-intervention rest period.<br>|
| Placebo Comparator: Warm water footbath<br>Footbath with warm water only | Other: Warm water only<br>* A ten-minute pre-intervention rest period followed by a 20-minute footbath with 12 l of warm water (40 °C), followed by a ten-minute post-intervention rest period.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-item warmth perception measure at the feet after the footbath | Self-reported warmth perception at both feet, assessed with the Herdecke warmth perception questionnaire immediately after the footbath (t2). Each item is scored 0-4 (0 = cold; 4 = hot), yielding a mean between 0 and 4. | Immediately after the footbath, timepoint 2 (t2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-item warmth perception measure at the feet at time point 1 (t1) and time point 3 (t3) | Self-reported warmth perception at both feet, assessed with the Herdecke warmth perception questionnaire immediately before (t1) and 10 minutes following the footbath (t3). Each item is scored 0-4 (0 = cold; 4 = hot), yielding a mean between 0 and 4. | Immediately before (time point 1, t1) and 10 minutes following the footbath (time point 3, t3). | 
| 2-item warmth perception measure at the hands at t1, t2 and t3 | Self-reported warmth perception at both hands, assessed with the Herdecke warmth perception questionnaire immediately before (t1), immediately after (t2) and 10 minutes following the footbath (t3). Each item is scored 0-4 (0 = cold; 4 = hot), yielding a mean between 0 and 4. | Immediately before (time point 1, t1), immediately after (time point 2, t2) and 10 minutes following the footbath (time point 3, t3). | 
| 2-item warmth perception measure at the head at t1, t2 and t3 | Self-reported warmth perception at the head, assessed with the Herdecke warmth perception questionnaire immediately before (t1), immediately after (t2) and 10 minutes following the footbath (t3). Each item is scored 0-4 (0 = cold; 4 = hot), yielding a mean between 0 and 4. | Immediately before (time point 1, t1), immediately after (time point 2, t2) and 10 minutes following the footbath (time point 3, t3) | 
| 1-item overall warmth perception measure at t1, t2 and t3 | Self-reported overall warmth perception, assessed with the Herdecke warmth perception questionnaire immediately before (t1), immediately after (t2) and 10 minutes following the footbath (t3). The item is scored 0-4 (0 = cold; 4 = hot). | Immediately before (time point 1, t1), immediately after (time point 2, t2) and 10 minutes following the footbath (time point 3, t3) | 
| Warmth perception and skin stimulus at the feet during the footbath | Self-reported perception of warmth and skin stimulus during the footbath, assessed with a dynamic warmth and skin stimulus visual analog scale (VAS), applied once per minute (0 = cold/no stimulus; 10 = very hot/very strong stimulus). | Up to 20 minutes | 
| Well-being at t1, t2 and t3 | Self-reported well-being, assessed with the Basler Befindlichkeits-Skala (Basel Mood Questionnaire, BBS) immediately before (t1), immediately after (t2) and 10 minutes following the footbath (t3). (BBS: 16 items; 7-point rating scale; higher values represent a better outcome.) | Immediately before (time point 1, t1), immediately after (time point 2, t2) and 10 minutes following the footbath (time point 3, t3) (length of footbath is up to 20 minutes) | 
| Skin surface temperature at the feet at t1, t2 and t3 | Skin surface temperature (°C) at both feet, measured with high-resolution infrared thermography immediately before (t1), immediately after (t2) and 10 minutes following the footbath (t3) | Immediately before (time point 1, t1), immediately after (time point 2, t2) and 10 minutes following the footbath (time point 3, t3) | 
| Skin surface temperature at the lower legs at t1, t2 and t3 | Skin surface temperature (°C) at both lower legs, measured with high-resolution infrared thermography immediately before (t1), immediately after (t2) and 10 minutes following the footbath (t3) | Immediately before (time point 1, t1), immediately after (time point 2, t2) and 10 minutes following the footbath (time point 3, t3) | 
| Skin surface temperature at the hands at t1, t2 and t3 | Skin surface temperature (°C) at both hands, measured with high-resolution infrared thermography immediately before (t1), immediately after (t2) and 10 minutes following the footbath (t3) | Immediately before (time point 1, t1), immediately after (time point 2, t2) and 10 minutes following the footbath (time point 3, t3) | 
| Skin surface temperature in the face at t1, t2 and t3 | Skin surface temperature (°C) in the face, measured with high-resolution infrared thermography immediately before (t1), immediately after (t2) and 10 minutes following the footbath (t3) | Immediately before (time point 1, t1), immediately after (time point 2, t2) and 10 minutes following the footbath (time point 3, t3) (length of footbath is up to 20 minutes) | 
| Heart rate variability (HRV) analysis: HF | HF: High frequency power band (0.15-0.40 Hz) (ms2) from frequency domain analysis, obtained from ECG recordings throughout the intervention and the pre- and post-intervention rest periods (VitaGuard® 3100 monitor, getemed, Germany) | Up to 40 minutes (continuous measurement from the beginning of the pre-intervention rest period to the end of the post-intervention rest-period) | 
| HRV analysis: LF | LF: Low frequency power band (0.04-0.15 Hz) (ms2) from frequency domain analysis (VitaGuard® 3100 monitor, getemed, Germany) | Up to 40 minutes (continuous measurement from the beginning of the pre-intervention rest period to the end of the post-intervention rest-period) | 
| HRV analysis: LF/HF ratio | LF/HF ratio = ratio of two bands from frequency domain analysis: LF band (0.04-0.15 Hz), HF band (0.15-0.40 Hz) (VitaGuard® 3100 monitor, getemed, Germany) | Up to 40 minutes (continuous measurement from the beginning of the pre-intervention rest period to the end of the post-intervention rest-period) | 
| HRV analysis: SDNN | SDNN: Standard deviation of normal to normal (NN) intervals (ms) (VitaGuard® 3100 monitor, getemed, Germany) | Up to 40 minutes (continuous measurement from the beginning of the pre-intervention rest period to the end of the post-intervention rest-period) | 
| HRV analysis: RMSSD | RMSSD: Root mean square of successive differences (ms) (VitaGuard® 3100 monitor, getemed, Germany) | Up to 40 minutes (continuous measurement from the beginning of the pre-intervention rest period to the end of the post-intervention rest-period) | 
| HRV analysis: pNN50 | pNN50: Percentage of successive NN intervals that differ from each other by more than 50 ms (%) (VitaGuard® 3100 monitor, getemed, Germany) | Up to 40 minutes (continuous measurement from the beginning of the pre-intervention rest period to the end of the post-intervention rest-period) | 
| Pulse wave analysis: Pulse Transit Time | Pulse Transit Time (PTT, ms), obtained from pulse oximetry recordings throughout the intervention and the pre- and post-intervention rest periods (VitaGuard® 3100 monitor, getemed, Germany) | Up to 40 minutes (continuous measurement from the beginning of the pre-intervention rest period to the end of the post-intervention rest-period) | 
| Pulse wave analysis: Reflection Index | Reflection Index (RI, %, percent), obtained from pulse oximetry recordings throughout the intervention and the pre- and post-intervention rest periods (VitaGuard® 3100 monitor, getemed, Germany) | Up to 40 minutes (continuous measurement from the beginning of the pre-intervention rest period to the end of the post-intervention rest-period) | 
| Pulse wave analysis: Perfusion Index | Perfusion Index (PI, %, percent), obtained from pulse oximetry recordings throughout the intervention and the pre- and post-intervention rest periods (VitaGuard® 3100 monitor, getemed, Germany) | Up to 40 minutes (continuous measurement from the beginning of the pre-intervention rest period to the end of the post-intervention rest-period) | 
| Evening morning protocol: perception of warmth and stimulus at the feet | Self-reported lasting effects of the footbaths at the feet, indicated on a seven-point rating scale (higher values represent a better outcome) | After footbath in the evening, before going to sleep; on the following morning, within 15 minutes after waking up | 
| Evening morning protocol: skin condition | Self-reported lasting effects of the footbaths on skin condition, indicated on a seven-point rating scale (higher values represent a better outcome) | After footbath in the evening, before going to sleep; on the following morning, within 15 minutes after waking up | 
| Evening morning protocol: general well-being | Self-reported lasting effects of the footbaths on general well-being, indicated on a seven-point rating scale (higher values represent a better outcome) | After footbath in the evening, before going to sleep; on the following morning, within 15 minutes after waking up | 
| Morning protocol: sleep quality: seven-point rating scale | Self-reported sleep quality during the night following the footbaths, indicated on a seven-point rating scale (higher values represent a better outcome) | In the morning after the footbath, within 15 minutes after waking up | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Mustard flour footbaths, Dose-response relationship, Thermogenesis, Infrared thermography, Heart rate variability, Healthy volunteers