Unloading Induced Effects on Local Glucose Uptake Into m. Soleus

Study Overview
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Brief Summary
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The present study aimed to investigate whether a daily intake of lupin protein and a neuromuscular electrical stimulation training twice a day can improve local glucose uptake into m. soleus during a 60 day unloading phase with a special unloading device, the HEPHAISTOS orthosis (HEP).

Detailed Description
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The 60 day unloading intervention with the HEPHAISTOS unloading device had the following key objectives: primary hypothesis: Assesment and evaluation of insulin sensitivity and local glucose uptake in the unloaded m. soleus and whether it can be improved by dietary supplementation of lupin seeds and neuromuscular electrical stimulation. secondary hypotheses: Assesment and evaluation of unloading-induced reductions in muscle mass and whether they can be mitigated by dietary supplementation of lupin seed and neuromuscular electrical stimulation. Assesment and evaluation of whole-body glycemic effects of the interventions.

Official Title
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Effects of Nutrition and Neuromuscular Electrical Stimulation on Local Glucose Uptake Into m. Soleus During 60 Days of Lower Leg Unloading

Conditions
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Local Glucose Uptake, Glucose Metabolism Disorders

Intervention / Treatment
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* Dietary Supplement: lupin protein
* Other: Neuromuscular electrical stimulation
* Device: HEPHAISTOS unloading orthotic device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male volunteers Age: between 20 and 45 years Body mass index (BMI): 20 -26 kg/m2 Agreement and signed consent before the study Exclusion Criteria: Smoker Competitive Athletes Diabetes mellitus Rheumatic disease Muscle or joint disease Bone fractures in the period up to one year before study start Herniated disc Flatfeet (pes planus) Allergy to nuts or legume Vascular diseases Epilepsy Severe hyperlipidemia Anemia (< Hb standard values; standard values healthy men: 13.5 -17.5 g/dl) * Increased thrombosis risk * Kidney disorder: deviations from normal values for creatinine in plasma. (Normal value: Creatinine < 1.20 mg/dl)* Lesions of the cruciate ligaments, or orthopedic surgery in the past 10 years on the side of the Hephaistos orthosis Achilles tendon injury, or rupture in the past 10 years on the side of the orthosis hyper-/hypocalcaemia (abnormal levels of calcium in the blood, normal level: 2.15 - 2.64 mmol/l) Intake of anti-inflammatory drugs during the study Abuse of drugs or alcohol (> than 20-30g alcohol/day) Participation in another clinical study within the last 2 months before the start of this study Increased bleeding tendency (hemophilia, regular use of anticoagulants) History of intolerance to local anesthetics Imprisoned during study Any other condition classed as unsuitable for study participation by the medical executive director prior convictions (objectionable criminal record) Additional Exclusion Criteria for MRI Metal implants or other osteosynthesis material Pacemaker Claustrophobia

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Group<br>Control Group consisting of six healthy male subjects wearing only the HEPHAISTOS ORTHOSIS for lower leg unloading (60 days). | Device: HEPHAISTOS unloading orthotic device<br>* Orthotic device which unloads the muscles of the lower leg. Subjects had to wear the device for the whole duration of the intervention phase (60 days).<br>* Other names: HEP;|
| Experimental: Intervention Group<br>Intervention group consisting of seven healthy mal subjects, wearing the HEPHAISTOS orthosis for lower leg unloading (60 days), plus receiving lupin protein every day and performing a neuromuscular electrical stimulation training twice a day. | Dietary Supplement: lupin protein<br>* 19g of lupin crunchy every day for the whole duration of the intervention phase (60 days)<br>Other: Neuromuscular electrical stimulation<br>* Individual neuromuscular electrical stimulation training had to be performed twice a day (morning and evening) over the whole duration of the intervention phase (60 days). Subjects were asked to continuously increase the intensity until a maximum intensity of 100mA per training.<br>* Other names: NMES;Device: HEPHAISTOS unloading orthotic device<br>* Orthotic device which unloads the muscles of the lower leg. Subjects had to wear the device for the whole duration of the intervention phase (60 days).<br>* Other names: HEP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Local Glucose Uptake into m. soleus | Biopsies were taken from m. soleus | Baseline to day 59 of the intervention phase | 
| Changes in Local Glucose Metabolism in m. soleus | Microdialysis was performed in m. soleus | Baseline to day 60 of the intervention phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Glucose (changes in the whole body glucose metabolism) |  | Baseline and day 2 & 1 before the intervention phase, day 4, 14, 28, 42 & 60 of the intervention phase and day 2 & 14 after the intervention phase | 
| Blood C-Peptide (changes in the whole body glucose metabolism) |  | Baseline and day 2 & 1 before the intervention phase, day 4, 14, 28, 42 & 60 of the intervention phase and day 2 & 14 after the intervention phase | 
| Blood HbA1c (changes in the whole body glucose metabolism) |  | Baseline and day 2 & 1 before the intervention phase, day 4, 14, 28, 42 & 60 of the intervention phase and day 2 & 14 after the intervention phase | 
| Blood Fructosamine (changes in the whole body glucose metabolism) |  | Baseline and day 2 & 1 before the intervention phase, day 4, 14, 28, 42 & 60 of the intervention phase and day 2 & 14 after the intervention phase | 
| Insulin Sensitivity (changes in the whole body glucose metabolism) | Whole body insulin sensitivity assessed by hyperinsulinemic euglycemic clamp | Baseline and day 60 of the intervention phase | 
| Changes in Muscle Volume | Muscle volume measured by magnetic resonance imaging (MRI) | Baseline to day 58 of the intervention phase | 
| Changes in Muscle Function (jump performance) | A jump test was performed | Baseline to day 58 of the intervention phase | 
| Changes in Muscle Function (MVC) | Maximal voluntary contractions (MVC) - isometric and isokinetic - were performed | Baseline to day 58 of the intervention phase | 
| Compliance | Electronic wearing time devices from Orthotimer were used to assess compliance of the subjects. | During 60 days of intervention | 
| Movement | Accelerometers were used to assess movement of the subjects. | During 60 days of intervention and during 14 days of the recovery phase (post intervention phase) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lupin Protein, Glucose Metabolism, GLUT4, Muscle Unloading, Neuromuscular Electrical Stimulation