Muscle AtrophyNCT03195348
The Effects of Whole Body Unloading on Physiological Function
A study testing HBF Bed Rest in people with Muscle Atrophy and Weightlessness, run by King's College London at 1 site in United Kingdom.
Trial summary
This study is a collaboration between the Centre of Human \& Aerospace Physiological Sciences (CHAPS) and the Sleep and Brain Plasticity Centre (Department of Neuroimaging) at King's College London and the Sleep Disorders Centre at Guy's Hospital.The main purpose of the study is to evaluate the effects of a 7 day… Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Muscle Atrophy, Weightlessness, Sleep Disturbance
- What is being tested?
- HBF Bed Rest
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 29 Mar 2017to 30 Aug 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males aged 18-40
- No clinically significant and relevant abnormalities in medical history
- Absence of any condition that could affect subject safety or well-being or their ability to understand and follow study procedures and requirements
- Absence of any condition which has/will result in irregular regulation of skeletal muscle, creatine metabolism or reduction of total skeletal muscle mass
- Absence of a medical history that includes back pain
Who cannot join
- Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients
- Habitual use (>twice a week) of creatine supplementation within 6 weeks of the study
- Previous history of smoking
- No known current or past neurological or psychiatric co-morbidities, no known sleep abnormalities (e.g. insomnia, snoring, sleep apnoea, sleep-walking/talking, nocturnal panic attacks, restless leg syndrome)
- Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit
- Relation of any study investigators, personnel at the study site or employee of any of the study sponsors
Show all 9Show fewer
- Any kind of medication prior to 1 month of screening
- Recent history (within the last 1 year) of alcohol or other substance abuse
- A previous history of nosebleeds
Trial locations and contacts
1 site in 1 country.
About this study
This study is a collaboration between the Centre of Human \& Aerospace Physiological Sciences (CHAPS) and the Sleep and Brain Plasticity Centre (Department of Neuroimaging) at King's College London and the Sleep Disorders Centre at Guy's Hospital.The main purpose of the study is to evaluate the effects of a 7 day unloading period (simulating micro gravity) on muscle mass using three independent methods; two scanning techniques (magnetic resonance imaging (MRI) and dual x-ray absorptiometry (DXA)) and one that involves swallowing a capsule that contains a harmless chemical called creatine (D3-Creatine (D3-cr)) and then measuring its concentration in urine. In order to induce muscle loss, participants will be required to lie flat on their back on a water bed filled with water and salt (called hyper-buoyancy flotation (HBF)). As this situation is similar to that experienced in space, the investigators will also measure the effect of HBF on sleep, brain and physiological function - all things known to change in astronauts. Sixteen male subjects (18-40 yrs) will be recruited to participate in the study that will require physiological testing before, during and following both 7 days of normal conditions and 7 days of HBF bed-rest. Each subject will be exposed to the same conditions and assessments over the study period. As some loss of muscle is expected, participants will be offered an exercise rehabilitation programme upon completion of HBF with self-monitored and/or guided sessions based on those provided by the Space Medicine Office of the European Space Agency to returning astronauts.
Read the detailed description
The rapid loss of skeletal muscle occurs in extreme physiological conditions, most notably within intensive care, hypoxia and during spaceflight. The cause of this accelerated loss is unknown; however, interventions aiming to slow the decline may have profound effects on quality of life post-surgery and, in space expedition terms, the ability to complete mission critical tasks. In addition, the current methodologies available to measure total skeletal muscle mass have limitations, lack accuracy (anthropometry and Bioelectrical Impedance Analysis (BIA)) or are immobile and costly (dual x-ray absorptiometry (DXA) and magnetic resonance imaging (MRI)).
The primary aim of this study is to investigate whole body skeletal muscle loss induced through 7 consecutive days of whole-body immobilisation using three independent methods; dual x-ray absorptiometry (DXA), magnetic resonance imaging (MRI) and D3-Creatine dilution (D3-cr). A number of secondary aims are also targeted, which have the shared objective to measure the impact of 7-days of immobilisation on HBF; 1. Muscular, neuromuscular and cardiovascular adaptation; 2. Neurophysiology, sleep architecture and cognition; 3. A range of spaceflight specific measures, aiming to characterise the intervention proposed within this study (hyper-buoyancy flotation (HBF) bed rest) as an alternative ground-based analogue to observe the physiological response to microgravity.
The muscular, neuromuscular and cardiovascular research is performed by King's College London Centre of Human \& Aerospace Physiological Sciences (KCL CHAPs) and ranges from measurement of whole-body change, to cellular adaptation. Total skeletal muscle mass will be measured using DXA, MRI and D3-cr as well as the cross-sectional area of a single muscle group (quadriceps) using ultrasound. A biopsy will be taken from the same muscle group (quadriceps) in order to investigate changes in muscle protein synthesis (MPS), myofibre size, force and protein: DNA ratio. Muscle performance will also be measured, from whole-body power output using a countermovement jump, to force expressed by the trunk, quadriceps, calf and handgrip. Muscle tone will be measured in three flexor and three extensor muscles in the calf, forearm and lower back. The plantarflexion muscles in the calf will be further assessed, with ankle proprioception, maximal strength and surface EMG of the medial gastrocnemius measured. Blood samples will be taken in order to distinguish changes in immunity and bone markers. The subject's height will be measured and intervertebral disc morphology distinguished using ultrasound and MRI.
The neuromuscular and muscle performance measurements will be obtained concurrently. Electrical activity produced by the skeletal muscles will be recorded and evaluated using electromyography (EMG). Prior to the force expression of the quadriceps being tested, pads will also be positioned for the muscle to be electrically stimulated and for a maximal involuntary force to be measured. Lastly, a cycle ergometer assessment will be undertaken, where power is ramped gradually and maximal aerobic utilisation (VO2max) determined.
The neurophysiology, sleep architecture and cognition investigation will be in collaboration with the Sleep and Brain Plasticity Centre (Department of Neuroimaging, IoPPN) and the Sleep Disorders Centre at Guy's Hospital. This study will look at any ensuing changes in sleep architecture and neurophysiology. Any associated cognitive or brain structural changes, which may be induced through 1 week of whole-body immobilisation, will also be investigated.
The procedures outlined are designed to assess known physiological adaptations occurring as a consequence of a micro-gravity environment, and therefore prove useful comparative tools from which the HBF model can be evaluated.
Sixteen male subjects (18-40 yrs) will be recruited to undertake test procedures pre- and post- a 7-day control period, where they will continue their habitual activities and be provided with their total (controlled) calorie intake, and pre- and post- a 7-day unloading period, where subjects will be required to remain on a hyper-buoyancy flotation (HBF) bed.
- Conditions
- Muscle Atrophy, Weightlessness, Sleep Disturbance, Astronaut-Bone Demineralisation Syndrome
- Being tested
- HBF Bed Rest
- Medical subject headings
- Muscular Atrophy, Parasomnias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HBF Bed RestOther
7 days of bed rest on hyper-buoyancy floatation (HBF)
| Study group | Role | What they receive |
|---|---|---|
| HBF Bed Rest | Experimental | 7 days control period followed by a washout period, then 7 days of HBF. Receives: Other: HBF Bed Rest |
What is being measured
The primary outcome is the main question the study is designed to answer.
Whole body skeletal muscle loss
The primary aim of this study is to investigate whole body skeletal muscle loss induced through 7 consecutive days of HBF using three independent methods; dual x-ray absorptiometry (DXA), magnetic resonance imaging (MRI) and D3-Creatine dilution (D3-cr)
Measured: 7 days
Secondary outcomes (13)
Regional differences in muscle loss
Regional (upper v lower limb) differences in muscle atrophy induced by HBF
Measured: 7 days
Relationship between change in total skeletal muscle mass and rectus femoris cross sectional area
To determine the relationship between change in total skeletal muscle mass (measured by MRI) and change in physiological cross sectional area (PCSA) of the rectus femoris as determined by ultrasound measurements of fascicle length and pennation angle.
Measured: 7 days
Central nervous system changes induced by 7-day HBF
To use neuroimaging, polysomnography and cognitive battery to investigate any structural (MR brain), neurophysiological (PSG/EEG) and functional (rs-fMRI and CANTAB battery test) central nervous system changes induced by the intervention
Measured: 7 days
Myofiber cross-sectional area changes with unloading compared with quadriceps cross sectional area
To determine the change in single muscle fibre cross-sectional area, using immunohistochemical staining, compared to total quadriceps cross-sectional area using ultrasound. Myofiber cross-sectional area will be measured using muscle biopsy tissue which will be mounted onto cork and cut into 5 μm-thick cryosections. Immunohistochemical stainings of muscle tissue cross sections will then measured using a microscope.
Measured: 7 days
Muscle biochemistry
To determine the change in biochemical (protein:DNA ratio) markers of quadriceps size in relation to the MRI and ultrasound measurements
Measured: 7 days
Change in fractional protein synthesis
To determine the relationship between change in quadriceps skeletal muscle mass (measured by MRI) and change in fractional protein synthesis (FPS) rate measured using tracer (D2O) techniques
Measured: 7 days
Changes in anabolic and catabolic signalling markers in muscle
To investigate changes of anabolic and catabolic signalling markers (such as MAFbx/atrogin-1 and MuRF1) in quadriceps muscle after 7 days HBF
Measured: 7 days
Changes in muscle function
To measure changes in muscle function as a result of 7 days HBF. These will include maximal voluntary isometric strength of the knee extensors, plantar flexors in the trunk and hand (hand grip) and explosive power during a countermovement jump.
Measured: 7 days
Changes in cardiorespiratory fitness
To measure changes in cardio respiratory fitness (maximal aerobic capacity (VO2max)) with 7 days of immobilisation
Measured: 7 days
Bone mineral density
To measure changes in bone mineral density (BMD) of before and after a 7 days HBF
Measured: 7 days
Plantarflexion strength
To determine the effect of 7 day HBF upon plantar flexion power output using an isokinetic dynamometer
Measured: 7 days
Muscle tone
To determine the effect of 7-day HBF upon the viscoelastic properties of superficial muscles and the Achilles tendon using Myoton.The viscoelastic properties of relaxed arm flexor, arm extensor, erector spinae, lateral gastrocnemius and Achilles tendon will be determined at rest (HBF) using the Myoton (hand-held myometer) on day 1, day 3, day 5 and day 7 (last day) of the HBF. This will be done by applying a short (15ms) and almost imperceptible mechanical impulse (force 0.4N) applied directly to the skin. The following parameters are derived from the oscillation acceleration signal generated by the mechanical impulse in real time by the Myoton's software: 1) Dynamic stiffness: which indicates the resistance to deformation of a tissue, 2) Oscillation frequency: which indicates the (muscle) tone or intrinsic tension of a tissue, 3) The logarithmic decrement of the oscillation: which characterises tissue elasticity.
Measured: 7 days
Functional re-adaptive exercise device (FRED)
To determine the ability, utility and potential efficacy of FRED following 7 days HBF
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2017
- Study start29 Mar 2017
- Primary completion30 Aug 2017
- Study completion30 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Muscle AtrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Collaborators
- Guy's and St Thomas' NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Ivana Rosenzweig, PhD, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03195348
- Sponsor's protocol ID
- 206237
- Status last verified
- Oct 2017
- First submitted
- 8 May 2017
- Last updated
- 31 Oct 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Whole Body Unloading on Physiological Function
- ClinicalTrials.gov ID
- NCT03195348
- Acronym / sponsor ID
- 206237
- Conditions
- Muscle Atrophy, Weightlessness, Sleep Disturbance, Astronaut-Bone Demineralisation Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Collaborators
- Guy's and St Thomas' NHS Foundation Trust
- Study start
- 29 Mar 2017 (actual)
- Primary completion
- 30 Aug 2017 (actual)
- Study completion
- 30 Aug 2017 (actual)
- First posted
- 22 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a collaboration between the Centre of Human \& Aerospace Physiological Sciences (CHAPS) and the Sleep and Brain Plasticity Centre (Department of Neuroimaging) at King's College London and the Sleep Disorders Centre at Guy's Hospital.The main purpose of the study is to evaluate the effects of a 7 day unloading period (simulating micro gravity) on muscle mass using three independent methods; two scanning techniques (magnetic resonance imaging (MRI) and dual x-ray absorptiometry (DXA)) and one that involves swallowing a capsule that contains a harmless chemical called creatine (D3-Creatine (D3-cr)) and then measuring its concentration in urine. In order to induce muscle loss, participants will be required to lie flat on their back on a water bed filled with water and salt (called hyper-buoyancy flotation (HBF)). As this situation is similar to that experienced in space, the investigators will also measure the effect of HBF on sleep, brain and physiological function - all things known to change in astronauts. Sixteen male subjects (18-40 yrs) will be recruited to participate in the study that will require physiological testing before, during and following both 7 days of normal conditions and 7 days of HBF bed-rest. Each subject will be exposed to the same conditions and assessments over the study period. As some loss of muscle is expected, participants will be offered an exercise rehabilitation programme upon completion of HBF with self-monitored and/or guided sessions based on those provided by the Space Medicine Office of the European Space Agency to returning astronauts.
Detailed description
The rapid loss of skeletal muscle occurs in extreme physiological conditions, most notably within intensive care, hypoxia and during spaceflight. The cause of this accelerated loss is unknown; however, interventions aiming to slow the decline may have profound effects on quality of life post-surgery and, in space expedition terms, the ability to complete mission critical tasks. In addition, the current methodologies available to measure total skeletal muscle mass have limitations, lack accuracy (anthropometry and Bioelectrical Impedance Analysis (BIA)) or are immobile and costly (dual x-ray absorptiometry (DXA) and magnetic resonance imaging (MRI)).
The primary aim of this study is to investigate whole body skeletal muscle loss induced through 7 consecutive days of whole-body immobilisation using three independent methods; dual x-ray absorptiometry (DXA), magnetic resonance imaging (MRI) and D3-Creatine dilution (D3-cr). A number of secondary aims are also targeted, which have the shared objective to measure the impact of 7-days of immobilisation on HBF; 1. Muscular, neuromuscular and cardiovascular adaptation; 2. Neurophysiology, sleep architecture and cognition; 3. A range of spaceflight specific measures, aiming to characterise the intervention proposed within this study (hyper-buoyancy flotation (HBF) bed rest) as an alternative ground-based analogue to observe the physiological response to microgravity.
The muscular, neuromuscular and cardiovascular research is performed by King's College London Centre of Human \& Aerospace Physiological Sciences (KCL CHAPs) and ranges from measurement of whole-body change, to cellular adaptation. Total skeletal muscle mass will be measured using DXA, MRI and D3-cr as well as the cross-sectional area of a single muscle group (quadriceps) using ultrasound. A biopsy will be taken from the same muscle group (quadriceps) in order to investigate changes in muscle protein synthesis (MPS), myofibre size, force and protein: DNA ratio. Muscle performance will also be measured, from whole-body power output using a countermovement jump, to force expressed by the trunk, quadriceps, calf and handgrip. Muscle tone will be measured in three flexor and three extensor muscles in the calf, forearm and lower back. The plantarflexion muscles in the calf will be further assessed, with ankle proprioception, maximal strength and surface EMG of the medial gastrocnemius measured. Blood samples will be taken in order to distinguish changes in immunity and bone markers. The subject's height will be measured and intervertebral disc morphology distinguished using ultrasound and MRI.
The neuromuscular and muscle performance measurements will be obtained concurrently. Electrical activity produced by the skeletal muscles will be recorded and evaluated using electromyography (EMG). Prior to the force expression of the quadriceps being tested, pads will also be positioned for the muscle to be electrically stimulated and for a maximal involuntary force to be measured. Lastly, a cycle ergometer assessment will be undertaken, where power is ramped gradually and maximal aerobic utilisation (VO2max) determined.
The neurophysiology, sleep architecture and cognition investigation will be in collaboration with the Sleep and Brain Plasticity Centre (Department of Neuroimaging, IoPPN) and the Sleep Disorders Centre at Guy's Hospital. This study will look at any ensuing changes in sleep architecture and neurophysiology. Any associated cognitive or brain structural changes, which may be induced through 1 week of whole-body immobilisation, will also be investigated.
The procedures outlined are designed to assess known physiological adaptations occurring as a consequence of a micro-gravity environment, and therefore prove useful comparative tools from which the HBF model can be evaluated.
Sixteen male subjects (18-40 yrs) will be recruited to undertake test procedures pre- and post- a 7-day control period, where they will continue their habitual activities and be provided with their total (controlled) calorie intake, and pre- and post- a 7-day unloading period, where subjects will be required to remain on a hyper-buoyancy flotation (HBF) bed.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HBF Bed Rest | Experimental | Other: HBF Bed Rest7 days control period followed by a washout period, then 7 days of HBF. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Males aged 18-40
- No clinically significant and relevant abnormalities in medical history
- Absence of any condition that could affect subject safety or well-being or their ability to understand and follow study procedures and requirements
- Absence of any condition which has/will result in irregular regulation of skeletal muscle, creatine metabolism or reduction of total skeletal muscle mass
- Absence of a medical history that includes back pain
Key exclusion criteria (9 listed)
- Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients
- Habitual use (>twice a week) of creatine supplementation within 6 weeks of the study
- Previous history of smoking
- No known current or past neurological or psychiatric co-morbidities, no known sleep abnormalities (e.g. insomnia, snoring, sleep apnoea, sleep-walking/talking, nocturnal panic attacks, restless leg syndrome)
- Participation in another clinical study or receipt of an investigational drug within 30 days of the screening visit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HBF Bed Rest7 days of bed rest on hyper-buoyancy floatation (HBF) | Other | HBF Bed Rest |
Primary outcome
Whole body skeletal muscle loss
Time frame: 7 days
The primary aim of this study is to investigate whole body skeletal muscle loss induced through 7 consecutive days of HBF using three independent methods; dual x-ray absorptiometry (DXA), magnetic resonance imaging (MRI) and D3-Creatine dilution (D3-cr)
13 secondary outcomes
Regional differences in muscle loss
Time frame: 7 days
Relationship between change in total skeletal muscle mass and rectus femoris cross sectional area
Time frame: 7 days
Central nervous system changes induced by 7-day HBF
Time frame: 7 days
Myofiber cross-sectional area changes with unloading compared with quadriceps cross sectional area
Time frame: 7 days
Muscle biochemistry
Time frame: 7 days
Change in fractional protein synthesis
Time frame: 7 days
Changes in anabolic and catabolic signalling markers in muscle
Time frame: 7 days
Changes in muscle function
Time frame: 7 days
Changes in cardiorespiratory fitness
Time frame: 7 days
Bone mineral density
Time frame: 7 days
Plantarflexion strength
Time frame: 7 days
Muscle tone
Time frame: 7 days
Functional re-adaptive exercise device (FRED)
Time frame: 7 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ivana Rosenzweig, PhD principal investigator
King's College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HBF Bed Rest in people with Muscle Atrophy and Weightlessness, run by King's College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Whole body skeletal muscle loss (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Oct 2017.