Prevention of knee Osteoarthritis in Overweight Females

ISRCTN	ISRCTN42823086
DOI	https://doi.org/10.1186/ISRCTN42823086
Protocol serial number	NTR679
Sponsor	Erasmus Medical Centre (Netherlands)
Funder	Netherlands Organisation for Health Research and Development

Submission date: 29/06/2006
Registration date: 29/06/2006
Last edited: 15/07/2019

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 is a condition that causes the joints to become painful and stiff. In the past few decades, research has identified the major risk factors for developing osteoarthritis of the knee. The next important step is to test preventive strategies in groups that are at high risk. Being overweight is the major modifiable risk factor for knee osteoarthritis. It is most often caused by unbalanced food intake in relation to physical activity, a way of life which is hard to change. To accomplish any change in such behaviour, a ‘tailor made’ diet and physical activity intervention is the most successful. However, an intervention with oral crystalline glucosamine sulphate, a chemical with growing scientific evidence for its joint-protective actions, is probably much easier and more feasible. In this study we will test the preventive effect of both interventions.

Who can participate?
Overweight women aged 50-60 (a high-risk group for knee osteoarthritis)

What does the study involve?
Participants are randomly allocated to either receive the tailor made weight loss intervention or to not receive this intervention. Secondly, in both groups half of the participants are randomly allocated to receive oral crystalline glucosamine sulphate while the other half receive a placebo (dummy drug). Both groups are followed for two and a half years. After two and a half years the occurrence of knee osteoarthritis is measured in both groups. After an additional 4-year observational period (i.e., 6.5 years after the start of the study), all available participants are re-evaluated.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Afdeling Huisartsgeneeskunde (Netherlands)

When is the study starting and how long is it expected to run for?
December 2005 to April 2012

Who is funding the study?
Netherlands Organisation for Health Research and Development

Who is the main contact?
Jos Runhaar
j.runhaar@erasmusmc.nl

Contact information

Mr Jos Runhaar
Scientific

Department of General Practice, Room NA1906
PO Box 2040
Rotterdam
3000 CA
Netherlands

Phone	+31 (0)10 704 4192
Email	j.runhaar@erasmusmc.nl

Study information

Primary study design	Interventional
Study design	Placebo-controlled 2 x 2 randomised factorial trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Prevention of knee Osteoarthritis in Overweight Females
Study acronym	PROOF
Study objectives	Amended as of 03/12/2008: In the present study we will test the preventive effect of a tailor made intervention for reducing weight as well as of an intervention with oral crystalline glucosamine sulphate in a factorial design in a high-risk group of overweight middle aged women who have not yet consulted for knee osteoarthritis. The positive outcomes with respect to feasibility of recruitement, compliance to the interventions, and low percentage of drop-out in the preceding feasibility trial led to the continuation of the study in this full-scale trial. This trial was preceded by a feasibility trial with recruitment dates December 2005 – April 2007. Initial information at time of registration: The present study is a feasibility study. In this study, we will test the feasibility of the procedures used, the compliance to the interventions, and the usefulness of intermediate outcome measures in a specific high-risk group. If the results of this feasibility study are satisfactory, the project will be upgraded into a full scale preventive trial.
Ethics approval(s)	Erasmus MC Medical Ethical Approval Commission, ref: 2005-231
Health condition(s) or problem(s) studied	Osteoarthritis in overweight females
Intervention	Patients are randomised for one of the following two interventions: Intervention group A: a tailor-made intervention to reduce weight under the direction of dieticians of homecare, Rotterdam for one year Control group A: the control group will not receive this active intervention to reduce weight Intervention group B: daily supplementation with glucosamine sulphate (1500 mg per day) for one year Control group B: the control group will receive a placebo
Intervention type	Mixed
Primary outcome measure(s)	Amended as of 03/12/2008: Difference between intervention and control group in: 1. Occurrence of radiological knee OA (Kellgren and Lawrence index two or more), or 2. Joint space narrowing of 1 mm or more in one of the knees during follow-up time, or 3. Occurrence of knee OA according to the American College of Rheumatology (ACR) criteria Initial information at time of registration: 1. Percentage of participants per group showing a reduction of 5 kg and/or 5% decrease at one year follow-up compared to baseline weight 2. Percentage of women compliant to the interventions in the study 3. Percentage lost to follow-up after one year 4. Percentage of eligible persons
Key secondary outcome measure(s)	Amended as of 03/12/2008: Difference between intervention and control group in: 1. Quality of life (Euroqol) 2. Knee pain and knee function (WOMAC) 3. Actual weight loss 4. Occurrence of knee osteoarthritis seen on MRI (scoring according to the KOSS protocol for the presence of cartilaginous lesions, osteophytes, subchondral cysts, bone marrow oedema, for meniscal abnormalities, presence and size of effusion, synovitis and Baker's cysts) 5. Increase of bone and cartilage degradation markers Initial information at time of registration: 1. Differences in intermediate outcomes between the intervention group A and control group A at one year follow-up 2. Differences in intermediate outcomes between intervention group B and control group B at one year follow-up 3. Change and variation in change in intermediate outcomes between baseline and one year follow-up.
Completion date	01/04/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Female
Target sample size at registration	400
Total final enrolment	407
Key inclusion criteria	Women aged 50 - 60 years who are overweight (body mass index [BMI] of 27 kg/m^2 or more)
Key exclusion criteria	Amended as of 03/12/2008: point six of the exclusion criteria has been amended as follows: 6. Contraindication for magnetic resonance (MR) imaging Initial information at time of registration: 1. Knee osteoarthritis (OA) 2. Knee pain indicating knee OA 3. Radiological signs indicating knee OA (Kellgren-Lawrence index of 2 or more) 4. Positive for knee OA according to the American College of Rheumatology (ACR) criteria for knee OA 5. Presence of severe co-morbidity 6. Pacemaker 7. Current use of glucosamine sulphate 8. Not being able to communicate in the Dutch language
Date of first enrolment	01/06/2008
Date of final enrolment	01/05/2009

Locations

Countries of recruitment

Netherlands

Study participating centre

Erasmus University Medical Center

Department of General Practice
PO Box 2040
Rotterdam
3000 CA
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/02/2014		Yes	No
Results article	results	01/08/2014		Yes	No
Results article	results	01/09/2014		Yes	No
Results article	results	01/10/2014		Yes	No
Results article	results	01/08/2015		Yes	No
Results article	results	01/08/2015		Yes	No
Results article	results	01/02/2016		Yes	No
Results article	results	01/04/2016		Yes	No
Results article	results	01/06/2016		Yes	No
Results article	results	01/07/2016		Yes	No
Results article	results	01/10/2016		Yes	No
Results article	results	01/08/2017		Yes	No
Results article	results	01/07/2019	15/07/2019	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

15/07/2019: Publication reference and total final enrolment added.
24/04/2017: Publication reference added.
20/06/2016: Plain English summary and publication references added.
17/06/2016: Publication reference added.
26/01/2016: Publication reference added.
03/12/2008: The following changes were made to this trial record:
1. The title of the trial was changed; the initial trial title was: 'Prevention of Osteoarthritis in Overweight Females'.
2. The overall trial end date was changed from 30/11/2007 to 01/04/2012.
3. The target number of participants was changed from 100 to 400.