Pycnogenol (maritime pine bark extract) in osteoarthritis

ISRCTN	ISRCTN10754119
DOI	https://doi.org/10.1186/ISRCTN10754119
Protocol serial number	N/A
Sponsor	Horphag Research LTD
Funder	Horphag Research LTD

Submission date: 07/10/2015
Registration date: 08/10/2015
Last edited: 15/02/2018

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Osteoarthritis (OA) is the most common type of arthritis, affecting millions of people worldwide. It occurs when the protective cartilage on the end of bones wears away. The bones then rub against one another, which can cause stiffness, pain and a reduction in a person’s range of movement. The knee is the most common joint to be affected by OA, and in severe cases, surgery may be the only treatment that can provide patients with relief. A knee arthroplasty, also known as knee replacement surgery, is recommended if the pain from OA is so severe that it is causing disability. In this operation, the diseased cartilage and bone is removed from the surface of the knee joint and replaced with a man-made surface of metal or plastic. This can happen on one side (partial) or both sides (total) of the knee joint, depending on how severe the damage is. Pycnogenol is the trade name of a dietary supplement made from French maritime pine bark extract. Previous studies have shown that it can help to relieve pain and joint stiffness in knee OA patients. Currently little is known about how it does this and whether components of the drug spread through the joints. The aim of this study is to find out how Pycnogenol works in patients with OA and how its components are spread throughout the body.

Who can participate?
Adults with severe knee osteoarthritis who are having knee replacement surgery.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive 200mg of Pycnogenol twice a day for three weeks before they are due to have their knee replacement surgery. Those in the second group do not receive any additional treatment in the three weeks leading up to their surgery. Blood samples are collected from all patients at the start of the study, 1-2 days before their surgery and just before/during their surgery, and joint fluid is taken on the day of the surgery. The blood and joint fluid are tested for markers that play a role inflammation and cartilage destruction of the joints.

What are the possible benefits and risks of participating?
There are no direct benefits or risks of participating in the study.

Where is the study run from?
Orthopedic Center for Musculoskeletal Research (Germany)

When is the study starting and how long is it expected to run for?
October 2012 to September 2014

Who is funding the study?
Horphag Research LTD (Cyprus)

Who is the main contact?
1. Professor Petra Högger (Scientific)
petra.hoegger@uni-wuerzburg.de
2. Dr Lothar Seefried (Public)
l.seefried.klh@uni-wuerzburg.de

Contact information

Prof Petra Högger
Scientific

Institut für Pharmazie und Lebensmittelchemie
Am Hubland C7
Würzburg
97074
Germany

Phone	+49 (0)931 318 5468
Email	petra.hoegger@uni-wuerzburg.de

Dr Lothar Seefried
Public

Orthopedic Center for Musculoskeletal Research, Department of Orthopedics
Brettreichstraße 11
Würzburg
97074
Germany

Phone	+49 (0)931 8030
Email	l.seefried.klh@uni-wuerzburg.de

Study information

Primary study design	Interventional
Study design	Single-centre randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	1. It is possible to detect constituents and/or metabolites of Pycnogenol in serum, blood cells and synovial fluid of patients after ingestion of the extract 2. Constituents and/or metabolites of Pycnogenol influence inflammatory and cartilage metabolism markers in osteoarthritis patients
Study objectives	After ingestion of Pycnogenol, components and/or metabolites of the extract are distributed into serum, blood cells and synovial fluid. Bioactive compounds in serum and synovial fluid exhibit molecular effects on key catabolic and inflammatory markers.
Ethics approval(s)	Local Ethics Committee of the Medical Faculty of the University Würzburg, 21/12/2011, ref: 248/11
Health condition(s) or problem(s) studied	Osteoarthritis
Intervention	Patients were randomized into two groups using a computer-generated randomization list which was not accessible to the physicians and nurses who were involved in the patient care and management. Half of the study participants (n= 15) were assigned to the treatment group receiving 200 mg of the French maritime pine bark extract Pycnogenol® per day (twice daily two capsules with each 50 mg) over three weeks prior to the planned surgery. The control group comprised of 15 patients who received no Pycnogenol®. Blood samples from each study participant were collected before oral intake of Pycnogenol® (V1, basal value); during the intake, approximately 1-2 days before the surgery (V2); and during or shortly before knee surgery (V3), about 12 h after the last dose of Pycnogenol®. On the day of the surgery residual knee cartilage and synovial fluid were also collected. There was no further follow-up.
Intervention type	Supplement
Primary outcome measure(s)	Detection and quantification of constituents and/or metabolites of Pycnogenol in serum, blood cells (before and after intake of Pycnogenol; V1, V2, V3) and synovial fluid (at the time of knee surgery, V3) of patients.
Key secondary outcome measure(s)	Measurement of markers of inflammation and cartilage metabolism in the patient's serum, blood cells (before and after intake of Pycnogenol; V1, V2, V3) and synovial fluid (at the time of knee surgery, V3) of patients, e.g. MMP-3, MMP-13, IL-1β, ADAMTS-5.
Completion date	30/09/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	30
Key inclusion criteria	1. Aged 18 years or over 2. Severe knee osteoarthritis according to the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score 3. Scheduled for an elective arthroplasty (Kellgren-Lawrence grade III-IV)
Key exclusion criteria	1. Taking Non-steroidal anti-inflammatory drugs (NSAIDs) or glucocorticoids within the past four weeks 2. Currently received a therapy with anti-coagulants 3. Tested positive for HIV, HCV or HCB 4. Have had a previous or current infection of the affected knee joint
Date of first enrolment	01/09/2012
Date of final enrolment	01/09/2014

Locations

Countries of recruitment

Germany

Study participating centres

Orthopedic Center for Musculoskeletal Research

Department of Orthopedics
Brettreichstraße 11
Würzburg
97074
Germany

Institute of Pharmacy and Food Chemistry (Institut für Pharmazie und Lebensmittelchemie)

Am Hubland C7
Würzburg
97074
Germany

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Other
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	16/12/2017		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

15/02/2018: Publication reference added.