Healthy
Conditions
Brief summary
The present study will investigate the impact of altered substrate availability on muscle atrophy, insulin sensitivity and muscle protein synthesis following short-term forearm immobilization
Detailed description
Thirty-six healthy young volunteers will undergo 2 days of forearm immobilization combined with ingestion of one of two drug or placebo. Before and after immobilization, they will receive a stable isotope tracer infusion (5.5 h) combined with repeated blood and muscle sampling under insulin clamp conditions, in order to measure insulin sensitivity and muscle protein synthesis in the fasted and fed state.
Interventions
BEHAVIORALForearm immobilization
Two days of forearm immobilization
Sponsors
Wellcome Trust
University of Exeter
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind study design
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Males and females 18-40 years of age * Body mass index between 18 and 27
Exclusion criteria
* Any diagnosed metabolic impairment (e.g. type 1 or 2 diabetes) * Any diagnosed cardiovascular disease * Hypertension (≥140 mmHg systolic and/or ≥90 mmHg diastolic) * Chronic use of any prescribed or over the counter pharmaceuticals (excluding oral contraceptives and contraceptive devices) * Regular use of nutritional supplements * Metallic implants * A personal or family history of thrombosis, epilepsy, seizures or schizophrenia * Any previous motor disorders * Any known disorders in lipid metabolism * Any known disorders in muscle metabolism * Known allergy for Acipimox, beta agonist, or other substances in the tablets * Known sensitivity for sympathomimetic drugs * Known hypokalaemia * Presence of an ulcer in the stomach or gut and/or strong history of indigestion * Known severe kidney problems * Pregnancy * Unable to give consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Forearm Glucose Uptake | During the steady-state phase of the insulin clamp (i.e. last 30 min) | Insulin sensitivity, measured as forearm glucose uptake, during a 30-min baseline period and hyperinsulinaemic-euglycaemic conditions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Muscle Protein Synthesis | In the fasted state (30 min before starting insulin clamp), and during the steady-state phase of the insulin clamp (i.e. last 30 min) | Percent change in muscle protein synthesis, measured as using the arteriovenous-venous method, via stable isotope tracer infusion |
Countries
United Kingdom
Participant flow
Pre-assignment details
A total of 57 participants were screened for their eligibility to taking part. n=6 were excluded, for the following reasons: n=5 BMI exceeding upper cut-off n=1 metabolic disease Of the remaining n=51, n=14 chose to not continue with the study. Of the remaining n=37, n=30 completed the study (n=3 data collection unsuccessful because of intravenous cannulation issues, n=4 dropped out)
Participants by arm
| Arm | Count |
|---|---|
| Acipimox Ingestion During Immobilization Oral ingestion of Acipimox during 2 days of forearm immobilization
Forearm immobilization: Two days of forearm immobilization | 10 |
| B-agonist During Immobilization Oral ingestion of salbutamol during 2 days of forearm immobilization
Forearm immobilization: Two days of forearm immobilization | 11 |
| Placebo Ingestion During Immobilization Oral ingestion of a placebo 2 days of forearm immobilization
Forearm immobilization: Two days of forearm immobilization | 9 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Cannulation issues | 0 | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Acipimox Ingestion During Immobilization | B-agonist During Immobilization | Placebo Ingestion During Immobilization | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 11 Participants | 9 Participants | 30 Participants |
| Age, Continuous | 21 years STANDARD_DEVIATION 3 | 23 years STANDARD_DEVIATION 4 | 23 years STANDARD_DEVIATION 7 | 22 years STANDARD_DEVIATION 5 |
| Body mass index | 22.9 kg^m2 STANDARD_DEVIATION 2.7 | 24.1 kg^m2 STANDARD_DEVIATION 3.5 | 23.9 kg^m2 STANDARD_DEVIATION 2.1 | 23.7 kg^m2 STANDARD_DEVIATION 2.8 |
| Diastolic blood pressure | 69 mmHg STANDARD_DEVIATION 6 | 70 mmHg STANDARD_DEVIATION 5 | 65 mmHg STANDARD_DEVIATION 6 | 68 mmHg STANDARD_DEVIATION 4 |
| Fat mass percentage | 20.9 percentage of body fat STANDARD_DEVIATION 9.4 | 24.4 percentage of body fat STANDARD_DEVIATION 12.1 | 25.1 percentage of body fat STANDARD_DEVIATION 9.2 | 23.5 percentage of body fat STANDARD_DEVIATION 10.2 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment United Kingdom | 10 participants | 11 participants | 9 participants | 30 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 5 Participants | 16 Participants |
| Systolic blood pressure | 117 mmHg STANDARD_DEVIATION 11 | 111 mmHg STANDARD_DEVIATION 9 | 114 mmHg STANDARD_DEVIATION 44 | 114 mmHg STANDARD_DEVIATION 10 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 11 | 0 / 9 |
| other Total, other adverse events | 1 / 10 | 4 / 11 | 1 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 11 | 0 / 9 |
Outcome results
Primary
Percent Change in Forearm Glucose Uptake
Insulin sensitivity, measured as forearm glucose uptake, during a 30-min baseline period and hyperinsulinaemic-euglycaemic conditions
Time frame: During the steady-state phase of the insulin clamp (i.e. last 30 min)
Population: All participants with completed data collection were included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acipimox Ingestion During Immobilization | Percent Change in Forearm Glucose Uptake | -73 Percent change in clamp FGU with immob | Standard Error 15 |
| B-agonist During Immobilization | Percent Change in Forearm Glucose Uptake | 127 Percent change in clamp FGU with immob | Standard Error 134 |
| Placebo Ingestion During Immobilization | Percent Change in Forearm Glucose Uptake | -95 Percent change in clamp FGU with immob | Standard Error 113 |
Secondary
Percent Change in Muscle Protein Synthesis
Percent change in muscle protein synthesis, measured as using the arteriovenous-venous method, via stable isotope tracer infusion
Time frame: In the fasted state (30 min before starting insulin clamp), and during the steady-state phase of the insulin clamp (i.e. last 30 min)
Population: All participants who completed data collection were included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acipimox Ingestion During Immobilization | Percent Change in Muscle Protein Synthesis | -93 Percent change in clamp phenylalanine Rd | Standard Error 40 |
| B-agonist During Immobilization | Percent Change in Muscle Protein Synthesis | -124 Percent change in clamp phenylalanine Rd | Standard Error 29 |
| Placebo Ingestion During Immobilization | Percent Change in Muscle Protein Synthesis | -251 Percent change in clamp phenylalanine Rd | Standard Error 145 |