The effect of peri-operative anti-inflammatory treatment on postoperative muscle weakness and muscle fatigue in elderly elective surgery patients

ISRCTN	ISRCTN51508868
DOI	https://doi.org/10.1186/ISRCTN51508868
Secondary identifying numbers	N/A

Submission date: 20/09/2011
Registration date: 09/11/2011
Last edited: 30/10/2012

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

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

Contact information

Prof Ivan Bautmans
Scientific

Laarbeeklaan 103
Brussels
1090
Belgium

Email	ivan.bautmans@vub.ac.be

Study information

Study design	Double blinded randomised placebo-controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
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
Study objectives	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(s)	Brussels University Hospital Medical Ethical Committee (Universitair Ziekenhuis Brussel)
Health condition(s) or problem(s) studied	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
Primary outcome measure	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 study start date	01/10/2011
Completion date	01/10/2013

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	Both
Target number of participants	N=100 (N=25 per treatment arm)
Key inclusion criteria	All elderly (male or female, aged > 60 years) elective abdominal surgery patients
Key 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
Date of first enrolment	01/10/2011
Date of final enrolment	01/10/2013

Locations

Countries of recruitment

Belgium

Study participating centre

Laarbeeklaan 103

Brussels
1090
Belgium

Sponsor information

Vrije University Brussels [Vrije Universiteit Brussel] (Belgium)
University/education

Frailty in Ageing Research Department
Laarbeeklaan 103
Brussels
1090
Belgium

Email	ivan.bautmans@vub.ac.be
Website	http://www.vub.ac.be/FRIA
"ROR"	https://ror.org/006e5kg04

Funders

Funder type

University/education

University of Brussels (Belgium)

No information available

Brussels University Hospital (Belgium)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Other publications		01/03/2010		Yes	No