Plain English Summary
Background and study aims
Recently, studies have shown that elderly patients tend to suffer more from muscle weakness and muscle fatigue post-surgery than compared to younger patients. Also, we found evidence that muscle fatigue caused by inflammation is due to local processes (such as muscle atrophy and loss of contractibility), acting at the muscle itself. The aim of this study is to evaluate how different treatments work to reduce postoperative muscle weakness and muscle fatigue in elderly elective abdominal surgery patients.
Who can participate?
All elderly (male or female, aged >60 years) elective abdominal surgery patients are eligible.
What does the study involve?
Participants will be randomly allocated to either one of three drugs (including a drug which is a tumour necrosis factor-alpha (TNF-a) inhibitor) or a dummy drug (placebo), before during and after surgery.
What are the possible benefits and risks of participating?
We expect that the treatment will reduce the postoperative muscle weakness and fatigue.
Patients will be excluded when contra-indications for the use of the study-medication exists. A recent study showed that TNF-a treatment did not increase the risk for surgical site infection.
Where is the study run from?
The leading centre is the Frailty in Aging research group of the Vrije Universiteit Brussel, in collaboration with the Universitair Ziekenhuis Brussel (University Hospital of the Vrije Universiteit Brussel), Belgium
When is the study starting and how long is it expected to run for?
October 2011 to September 2013.
Who is funding the study?
Frailty in Ageing research group of the Vrije Universiteit Brussel, in collaboration with the Universitair Ziekenhuis Brussel (University Hospital of the Vrije Universiteit Brussel), Belgium
Who is the main contact?
Dr Ivan Bautmans
ivan.bautmans@vub.ac.be
Trial website
Contact information
Type
Scientific
Primary contact
Prof Ivan Bautmans
ORCID ID
Contact details
Laarbeeklaan 103
Brussels
1090
Belgium
ivan.bautmans@vub.ac.be
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
The effect of peri-operative anti-inflammatory treatment on postoperative muscle weakness and muscle fatigue in elderly elective surgery patients: a double blinded randomized placebo-controlled trial
Acronym
Study hypothesis
Could Pharmacological interventions designed to prevent inflammation-induced structural changes in the skeletal muscle reduce postoperative muscle weakness and muscle fatigue in elderly elective abdominal surgery patients?
Ethics approval
Brussels University Hospital Medical Ethical Committee (Universitair Ziekenhuis Brussel)
Study design
Double blinded randomised placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Post-operative muscle weakness, fatigue and inflammation
Intervention
Three different pharmacological interventions, each counter-acting different steps of the inflammation-induced proteolytic pathway in skeletal muscle, will be compared to placebo control:
1. Tumor necrosis factor-alpha (TNF-a) inhibitor [50mg Etanercept by subcutaneous (SC) injection 1 day preoperative, N=25)
2. Calpain inhibitor (16mg Molsidomine daily by mouth (per os), starting 1 day preoperative until 1 week postoperative, N=25)
3. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-eB) downregulator (267mg Fenofibrate daily, starting 1 day preoperative until 1 week postoperative N=25)
4. Placebo control (N=25)
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measures
1. Muscle performance: Maximal handgrip strength, muscle fatigue resistance and grip work will be assessed one day before surgery, and 2, 4, 8 and 30 days post-surgery
2. Self-perceived fatigue and pain: self-perceived fatigue (Fatigue subscale of the Profile of Mood State) and pain (Visual Analogue Scale) will be assessed one day before surgery, and 2, 4, 8 and 30 days post-surgery
3. Inflammation: circulating levels of pro- and anti-inflammatory cytokines and their intra-cellular gene expression in Peripheral Mononuclear Blood Cells. Overnight fasting serum samples will be collected from the non-dominant arm at one day before surgery, and 2, 4, 8 and 30 days post-surgery.
Secondary outcome measures
Occurrence of adverse reactions and postoperative complications:
All participants will be questioned and monitored for adverse reactions (potentially related to the study medication, i.e. allergies, headache, hypotension) at day 2, 4, 8 and 30 post-surgery.
Occurrence of postoperative complications will be extracted from the patients medical record.
Overall trial start date
01/10/2011
Overall trial end date
01/10/2013
Reason abandoned
Eligibility
Participant inclusion criteria
All elderly (male or female, aged > 60 years) elective abdominal surgery patients
Participant type
Patient
Age group
Senior
Gender
Both
Target number of participants
N=100 (N=25 per treatment arm)
Participant exclusion criteria
1. Unavailable one day before the surgical intervention
2. Presenting important inflammation preoperatively C-reactive protein (CRP)>10mg/L
3. Unable to understand or execute the test instructions due to cognitive impairment mini mental state examination (MMSE<23 / 30) and/or physical disability
4. Already using selective tumor necrosis factor (TNF)-alpha inhibitors, nitric oxide donors, fibrates, non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids or when contra-indications for the use of one of these products exist
Recruitment start date
01/10/2011
Recruitment end date
01/10/2013
Locations
Countries of recruitment
Belgium
Trial participating centre
Laarbeeklaan 103
Brussels
1090
Belgium
Sponsor information
Organisation
Vrije University Brussels [Vrije Universiteit Brussel] (Belgium)
Sponsor details
Frailty in Ageing Research Department
Laarbeeklaan 103
Brussels
1090
Belgium
ivan.bautmans@vub.ac.be
Sponsor type
University/education
Website
Funders
Funder type
University/education
Funder name
University of Brussels (Belgium)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Brussels University Hospital (Belgium)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
http://www.ncbi.nlm.nih.gov/pubmed/19808837
Publication citations
-
Bautmans I, Njemini R, De Backer J, De Waele E, Mets T, Surgery-induced inflammation in relation to age, muscle endurance, and self-perceived fatigue., J. Gerontol. A Biol. Sci. Med. Sci., 2010, 65, 3, 266-273, doi: 10.1093/gerona/glp145.