Condition category
Musculoskeletal Diseases
Date applied
29/06/2006
Date assigned
29/06/2006
Last edited
22/06/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

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

Trial website

Contact information

Type

Scientific

Primary contact

Mr Jos Runhaar

ORCID ID

Contact details

Department of General Practice
Room NA1906
PO Box 2040
Rotterdam
3000 CA
Netherlands
+31 (0)10 704 4192
j.runhaar@erasmusmc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

NTR679

Study information

Scientific title

Prevention of knee Osteoarthritis in Overweight Females

Acronym

PROOF

Study hypothesis

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

Erasmus MC Medical Ethical Approval Commission, ref: 2005-231

Study design

Placebo-controlled 2 x 2 randomised factorial trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

GP practices

Trial type

Prevention

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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

Phase

Drug names

Primary outcome measures

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

Secondary outcome measures

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.

Overall trial start date

01/12/2005

Overall trial end date

01/04/2012

Reason abandoned

Eligibility

Participant inclusion criteria

Women aged 50 - 60 years who are overweight (body mass index [BMI] of 27 kg/m^2 or more)

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

400

Participant 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

Recruitment start date

01/06/2008

Recruitment end date

01/05/2009

Locations

Countries of recruitment

Netherlands

Trial participating centre

Erasmus University Medical Center
Department of General Practice PO Box 2040
Rotterdam
3000 CA
Netherlands

Sponsor information

Organisation

Erasmus Medical Centre (Netherlands)

Sponsor details

Department of General Practice
PO Box 2040
Rotterdam
3000 CA
Netherlands

Sponsor type

Hospital/treatment centre

Website

www.erasmusmc.nl/huisartsgeneeskunde/research/

Funders

Funder type

Research organisation

Funder name

Netherlands Organisation for Health Research and Development

Alternative name(s)

Netherlands Organisation for Health Research and Development

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

Netherlands

Results and Publications

Publication and dissemination plan

Results of the first 2.5 years of the PROOF Study will be published from 2012 – 2015
Results of MRI data will be published from 2015 – 2017
Results of the complete follow-up time will be published from 2016 – 2017

Intention to publish date

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/23429925
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24774470
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24706992
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25278062
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25891749
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25818496
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26806185
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/27305950
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26866630
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26521011
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26748391

Publication citations

Additional files

Editorial Notes

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.