Metabolic and Muscular Adaptations During Inactivity in 3 Days of Bed-rest

NCT03495128 | Completed

• 2 other identifiers: 6-1704BB/P005004/1
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Muscle Atrophy; Insulin Sensitivity

Keywords

muscle protein breakdown; inactivity; bed rest

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (18)

• Change in Insulin stimulated whole body glucose uptake

  after 3 days of reconditioning, compared to post-bed rest

• Change in Insulin stimulated leg glucose uptake

  after 3 days of bed rest, compared to pre-bed rest

• Change in Insulin stimulated leg glucose uptake

  after 3 days of reconditioning, compared to post- bedrest

• Change in Whole body muscle mass

  after 3 days of bed rest, compared to pre-bed rest

• Change in Whole body muscle mass

  after 3 days of reconditioning, compared to post- bed rest

Study Arms (2)

Bed rest

EXPERIMENTAL

Three days of bed rest at -6 degrees of head-down tilt

Other: Bed Rest

Reconditioning

EXPERIMENTAL

Three days of one-legged knee extension contractions to recondition one leg

Other: Reconditioning

Interventions

Bed Rest OTHER

3 days of head down tilt (-6 degrees) bed rest

Bed rest

Reconditioning OTHER

daily resistance training (for 3 days) on one leg

Reconditioning

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

David Greenfield Human Physiology Laboratories

Nottingham, Notts, NG72UH, United Kingdom

Location

Related Publications (5)

• Bergouignan A, Rudwill F, Simon C, Blanc S. Physical inactivity as the culprit of metabolic inflexibility: evidence from bed-rest studies. J Appl Physiol (1985). 2011 Oct;111(4):1201-10. doi: 10.1152/japplphysiol.00698.2011. Epub 2011 Aug 11.

  PMID: 21836047 BACKGROUND

• 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.

  PMID: 22818936 BACKGROUND

• 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.

  PMID: 382871 BACKGROUND

• 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.

  PMID: 27654940 BACKGROUND

• 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 disposal and fuel utilization. J Cachexia Sarcopenia Muscle. 2022 Dec;13(6):2999-3013. doi: 10.1002/jcsm.13075. Epub 2022 Sep 4.

  PMID: 36058634 RESULT

MeSH Terms

Conditions

Muscular Atrophy; Insulin Resistance; Sedentary Behavior

Interventions

Bed Rest

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Behavior

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Paul L Greenhaff, PhD

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Research Fellow

Model Details: longitudinal assessment

Study Record Dates

• First Submitted: March 30, 2018
• First Posted: April 11, 2018
• Study Start: January 8, 2018
• Primary Completion: July 31, 2018
• Study Completion: December 31, 2019
• Last Updated: January 3, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)