ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 86 of 97 for:    calcium cation

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03495128
Recruitment Status : Active, not recruiting
First Posted : April 11, 2018
Last Update Posted : October 23, 2018
Sponsor:
Information provided by (Responsible Party):
Elizabeth Simpson, University of Nottingham

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.

Condition or disease Intervention/treatment Phase
Muscle Atrophy Insulin Sensitivity Other: Bed Rest Other: Reconditioning Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: longitudinal assessment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : January 8, 2018
Actual Primary Completion Date : July 31, 2018
Estimated Study Completion Date : March 31, 2019

Arm Intervention/treatment
Experimental: Bed rest
Three days of bed rest at -6 degrees of head-down tilt
Other: Bed Rest
3 days of head down tilt (-6 degrees) bed rest

Experimental: Reconditioning
Three days of one-legged knee extension contractions to recondition one leg
Other: Reconditioning
daily resistance training (for 3 days) on one leg




Primary Outcome Measures :
  1. Change in Insulin stimulated whole body glucose uptake [ Time Frame: after 3 days of bed rest, compared to pre-bed rest ]
    Determined during a hyperinsulinemic, euglycemic clamp


Secondary Outcome Measures :
  1. Change in Insulin stimulated whole body glucose uptake [ Time Frame: after 3 days of reconditioning, compared to post-bed rest ]
    Determined during a hyperinsulinemic, euglycemic clamp

  2. Change in Insulin stimulated leg glucose uptake [ Time Frame: after 3 days of bed rest, compared to pre-bed rest ]
    Determined during a hyperinsulinemic, euglycemic clamp, using arterialised-venous vs. venous difference in glucose concentration and ultrasound derived femoral artery blood flow

  3. Change in Insulin stimulated leg glucose uptake [ Time Frame: after 3 days of reconditioning, compared to post- bedrest ]
    Determined during a hyperinsulinemic, euglycemic clamp, using arterialised-venous vs. venous difference in glucose concentration and ultrasound derived femoral artery blood flow

  4. Change in Whole body muscle mass [ Time Frame: after 3 days of bed rest, compared to pre-bed rest ]
    Determined using whole body magnetic resonance imaging

  5. Change in Whole body muscle mass [ Time Frame: after 3 days of reconditioning, compared to post- bed rest ]
    Determined using whole body magnetic resonance imaging

  6. Change in Muscle Pyruvate dehydrogenase activity [ Time Frame: after 3 days of bed rest, compared to pre-bed rest ]
    Determined biochemically from vastus lateralis muscle biopsy samples before (fasting state) and at the end of the 3hr hyperinsulinemic, euglycemic clamp (insulin stimulated state).

  7. Change in Muscle Pyruvate dehydrogenase activity [ Time Frame: after 3 days of reconditioning, compared to post- bed rest ]
    Determined biochemically from vastus lateralis muscle biopsy samples before (fasting state) and at the end of the 3hr hyperinsulinemic, euglycemic clamp (insulin stimulated state).

  8. Change in Muscle gene expression [ Time Frame: after 3 days of bed rest, compared to pre-bed rest ]
    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)

  9. Change in Muscle gene expression [ Time Frame: after 3 days of reconditioning, compared to post-bed rest ]
    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)

  10. Change in Muscle protein turnover [ Time Frame: after 3 days of bed rest, compared to pre- bedrest ]
    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)

  11. Change in muscle triglyceride content [ Time Frame: after 3 days of bed rest, compared to pre-bed rest ]
    Determined using mid-thigh magnetic resonance spectroscopy

  12. Change in muscle triglyceride content [ Time Frame: after 3 days of reconditioning, compared to post-bed rest ]
    Determined using mid-thigh magnetic resonance spectroscopy

  13. Change in liver triglyceride content [ Time Frame: after 3 days of bed rest, compared to pre-bed rest ]
    Determined using magnetic resonance spectroscopy of the liver

  14. Change in liver triglyceride content [ Time Frame: after 3 days of reconditioning, compared to post-bed rest ]
    Determined using magnetic resonance spectroscopy of the liver

  15. Change in Markers of bone turnover [ Time Frame: after 3 days of bed rest, compared to pre-bed rest ]
    biochemical analysis of blood and urine; procollagen I protein, Calcium, Albumin, ionized calcium, Parathyroid hormone, Dickkopf-1, Sclerostin, carboxy-terminal collagen crosslinks, Osteocalcin

  16. Change in Markers of bone turnover [ Time Frame: after 3 days of reconditioning, compared to post-bed rest ]
    biochemical analysis of blood and urine; procollagen I protein, Calcium, Albumin, ionized calcium, Parathyroid hormone, Dickkopf-1, Sclerostin, carboxy-terminal collagen crosslinks, Osteocalcin

  17. change in adipose tissue function [ Time Frame: after 3 days of bed rest, compared to pre-bed rest ]
    biochemical analysis of blood; Adiponectin, Leptin, Visfatin, Resistin

  18. change in adipose tissue function [ Time Frame: after 3 days of reconditioning, compared to post-bed rest ]
    biochemical analysis of blood; Adiponectin, Leptin, Visfatin, Resistin



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03495128


Locations
United Kingdom
David Greenfield Human Physiology Laboratories
Nottingham, Notts, United Kingdom, NG72UH
Sponsors and Collaborators
University of Nottingham
Investigators
Principal Investigator: Paul L Greenhaff, PhD University of Nottingham

Publications:
Responsible Party: Elizabeth Simpson, Senior Research Fellow, University of Nottingham
ClinicalTrials.gov Identifier: NCT03495128     History of Changes
Other Study ID Numbers: 6-1704
BB/P005004/1 ( Other Grant/Funding Number: BBSRC )
First Posted: April 11, 2018    Key Record Dates
Last Update Posted: October 23, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Elizabeth Simpson, University of Nottingham:
muscle protein breakdown
inactivity
bed rest

Additional relevant MeSH terms:
Atrophy
Insulin Resistance
Muscular Atrophy
Pathological Conditions, Anatomical
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms