Insulin Sensitivity Clinical Trial
Official title:
Determination of the Time-course of Development of Insulin Resistance, and Associated Molecular and Muscular Adaptations, During Inactivity in 3 Days of Bed-rest
Verified date | February 2023 |
Source | University of Nottingham |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Space flight is associated with detrimental changes to the human body, including bone and muscle loss, fluid changes and deconditioning of muscles in the heart and blood vessels. Bed rest experiments, on Earth, are used to study these changes in healthy volunteers, as the disuse of muscles, and impact on the body, mimic the changes seen in the low-gravity environment of Space. Moreover, these changes are similar to those reported in people who remain in bed for long periods of time, such as is seen in intensive care or stroke patients, and bed rest studies also allow the physiological and biochemical impacts of this confinement to be investigated. For example, we know from previous research that muscle inactivity can lead to the development of resistance to the action of the hormone 'insulin', which is a longer term risk factor for the development of type 2 diabetes. Previous studies suggest that this inactivity-induced insulin resistance occurs within the first 48 hours of immobilization. However, it is not clear whether the biochemical and physiological processes underlying these short-term responses to inactivity are the same as those seen in the longer term. The current study aims to investigate the biochemical and physiological changes seen after 3 days of bed rest and to compare to those measured in a previous 57 days bed rest study carried out at Institut Médecine Physiologie Spatiale (MEDES; Toulouse, France). A 3-day period of reconditioning will subsequently be used to determine if these changes can be readily reversed.
Status | Completed |
Enrollment | 10 |
Est. completion date | December 31, 2019 |
Est. primary completion date | July 31, 2018 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | Male |
Age group | 20 Years to 45 Years |
Eligibility | Inclusion Criteria: - Physically and mentally healthy participants - Body mass index 20 - 26 kg/m2 - Height 158 - 190 cm (62 - 75 inches), - Participants that are able to consent to participation in the entire study - Signed informed consent Exclusion Criteria: - regular use of prescribed or 'over-the counter' medication - Bone mineral density (measured by Dual-Energy X-ray Absorptiometry) more than 1.5 standard deviation less than t-score - Family history of thrombosis or positive response in thrombosis blood screening: Antithrombin III, High sensitive C-Reactive Protein, protein kinase B, F-V-Leiden, Prothrombin mutation, Lupus-prothrombin time, Factor II - Any current medical condition - A medical history of thyroid dysfunction, renal function disorder (including renal stones), diabetes, cardiac arrhythmias and cardiovascular disorders, migraines, allergies, hypertension, hypocalcaemia, uric acidaemia, lipidemia or hyperhomocysteinemia, hiatus hernia, bowel surgery or gastro-oesophageal reflux - History of a mental health disorder - Smoker within six months prior to the start of the study - Dependence on drugs, medicine or alcohol - History of orthostatic intolerance, vestibular disorders or claustrophobia - Special food diet, vegetarian or vegan, history of intolerance to lactose or food allergy, - Osteosynthesis material, presence of metallic implants, history of knee problems or joint surgery/broken leg, - Orthopaedic or musculoskeletal disorders. |
Country | Name | City | State |
---|---|---|---|
United Kingdom | David Greenfield Human Physiology Laboratories | Nottingham | Notts |
Lead Sponsor | Collaborator |
---|---|
University of Nottingham |
United Kingdom,
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Brook MS, Wilkinson DJ, Mitchell WK, Lund JN, Phillips BE, Szewczyk NJ, Greenhaff PL, Smith K, Atherton PJ. Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans. J Physiol. 2016 Dec 15;594(24):7399-7417. doi: 10.1113/JP272857. Epub 2016 Nov 7. — View Citation
DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979 Sep;237(3):E214-23. doi: 10.1152/ajpendo.1979.237.3.E214. — View Citation
Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT; Lancet Physical Activity Series Working Group. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet. 2012 Jul 21;380(9838):219-29. doi: 10.1016/S0140-6736(12)61031-9. — View Citation
Shur NF, Simpson EJ, Crossland H, Chivaka PK, Constantin D, Cordon SM, Constantin-Teodosiu D, Stephens FB, Lobo DN, Szewczyk N, Narici M, Prats C, Macdonald IA, Greenhaff PL. Human adaptation to immobilization: Novel insights of impacts on glucose disposa — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in Insulin stimulated whole body glucose uptake | Determined during a hyperinsulinemic, euglycemic clamp | after 3 days of bed rest, compared to pre-bed rest | |
Secondary | Change in Insulin stimulated whole body glucose uptake | Determined during a hyperinsulinemic, euglycemic clamp | after 3 days of reconditioning, compared to post-bed rest | |
Secondary | Change in Insulin stimulated leg glucose uptake | Determined during a hyperinsulinemic, euglycemic clamp, using arterialised-venous vs. venous difference in glucose concentration and ultrasound derived femoral artery blood flow | after 3 days of bed rest, compared to pre-bed rest | |
Secondary | Change in Insulin stimulated leg glucose uptake | Determined during a hyperinsulinemic, euglycemic clamp, using arterialised-venous vs. venous difference in glucose concentration and ultrasound derived femoral artery blood flow | after 3 days of reconditioning, compared to post- bedrest | |
Secondary | Change in Whole body muscle mass | Determined using whole body magnetic resonance imaging | after 3 days of bed rest, compared to pre-bed rest | |
Secondary | Change in Whole body muscle mass | Determined using whole body magnetic resonance imaging | after 3 days of reconditioning, compared to post- bed rest | |
Secondary | Change in Muscle Pyruvate dehydrogenase activity | Determined biochemically from vastus lateralis muscle biopsy samples before (fasting state) and at the end of the 3hr hyperinsulinemic, euglycemic clamp (insulin stimulated state). | after 3 days of bed rest, compared to pre-bed rest | |
Secondary | Change in Muscle Pyruvate dehydrogenase activity | Determined biochemically from vastus lateralis muscle biopsy samples before (fasting state) and at the end of the 3hr hyperinsulinemic, euglycemic clamp (insulin stimulated state). | after 3 days of reconditioning, compared to post- bed rest | |
Secondary | Change in Muscle gene expression | expression of genes related to protein turnover, fuel metabolism, in muscle biopsy samples from vastus lateralis taken before (fasting state) and at the end of the 3hr hyperinsulinemic, euglycemic clamp (insulin stimulated state) | after 3 days of bed rest, compared to pre-bed rest | |
Secondary | Change in Muscle gene expression | expression of genes related to protein turnover, fuel metabolism, in muscle biopsy samples from vastus lateralis taken before (fasting state) and at the end of the 3hr hyperinsulinemic, euglycemic clamp (insulin stimulated state) | after 3 days of reconditioning, compared to post-bed rest | |
Secondary | Change in Muscle protein turnover | oral administration of stable isotopes Methyl-D3-3 methylhistidine, D3 creatine and D2O will be used to assess muscle protein breakdown and muscle protein synthesis (urine, saliva, blood and muscle biopsy analysis) | after 3 days of bed rest, compared to pre- bedrest | |
Secondary | Change in muscle triglyceride content | Determined using mid-thigh magnetic resonance spectroscopy | after 3 days of bed rest, compared to pre-bed rest | |
Secondary | Change in muscle triglyceride content | Determined using mid-thigh magnetic resonance spectroscopy | after 3 days of reconditioning, compared to post-bed rest | |
Secondary | Change in liver triglyceride content | Determined using magnetic resonance spectroscopy of the liver | after 3 days of bed rest, compared to pre-bed rest | |
Secondary | Change in liver triglyceride content | Determined using magnetic resonance spectroscopy of the liver | after 3 days of reconditioning, compared to post-bed rest | |
Secondary | Change in Markers of bone turnover | biochemical analysis of blood and urine; procollagen I protein, Calcium, Albumin, ionized calcium, Parathyroid hormone, Dickkopf-1, Sclerostin, carboxy-terminal collagen crosslinks, Osteocalcin | after 3 days of bed rest, compared to pre-bed rest | |
Secondary | Change in Markers of bone turnover | biochemical analysis of blood and urine; procollagen I protein, Calcium, Albumin, ionized calcium, Parathyroid hormone, Dickkopf-1, Sclerostin, carboxy-terminal collagen crosslinks, Osteocalcin | after 3 days of reconditioning, compared to post-bed rest | |
Secondary | change in adipose tissue function | biochemical analysis of blood; Adiponectin, Leptin, Visfatin, Resistin | after 3 days of bed rest, compared to pre-bed rest | |
Secondary | change in adipose tissue function | biochemical analysis of blood; Adiponectin, Leptin, Visfatin, Resistin | after 3 days of reconditioning, compared to post-bed rest |
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