Comparison between intraarticular ozone and a placebo in the treatment of knee arthritis

Plain English Summary

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. One of the most common joints to be affected is the knee, and in many sufferers, the pain prevents people from moving around leading to muscle weakness and disability. There are a variety of treatments for knee OA, including exercise, medication and surgery (knee replacement). One promising new treatment is the injection of ozone into the knee joint to help alleviate pain. Ozone is a gas made up of three atoms of oxygen joined together, rather than the usual two atoms as found in the oxygen we breathe from the air. The aim of this study is to find out whether ozone injections into the affected knee joint are an effective treatment for knee OA.

Who can participate?
Patients aged between 60 and 85 who have knee OA.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive eight, weekly injections of ozone into the knee joint. Those in the second group have a placebo (dummy), consisting of normal air injected into the knee joint. At the start of the study and then again after four week, eight weeks and two months, patients in both groups have their pain levels assessed using a range of questionnaires.

What are the possible benefits and risks of participating?
Participants who receive the ozone injections may benefit from an improvement to their pain levels and OA symptoms. There is a small risk of pain in the knee during and after injections.

Where is the study run from?
1. Paulista School of Medicine – Federal University of São Paulo (Brazil)
2. Pró-Vida – Center for Total Health Assistance LLC (Brazil)
3. University of Santo Amaro – Medicine College (Brazil)

When is the study starting and how long is it expected to run for?
February 2010 to June 2015

Who is funding the study?
Sao Paolo Medical School (Brazil)

Who is the main contact?
Professor Carlos César Lopes de Jesus
caceloje@gmail.com

Trial website

Type

Scientific

Primary contact

Prof Carlos César Lopes de Jesus

ORCID ID

Contact details

Rua Pedro de Toledo
598
São Paulo
04039-001
Brazil
+55 (0)11 55752970 / 50850248
caceloje@gmail.com

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

NCT29102010

Scientific title

Comparison between intraarticular ozone and a placebo in the treatment of knee arthritis: A double blind, randomised placebo controlled trial

Acronym

INOPKA

Study hypothesis

Hypothesis as of 30/12/2016:
Ozone is more effective than a placebo in the treatment of knee osteoarthritis concerning pain relief, improvement of joint function and quality of life.

Original hypothesis:
Ozone is more affective than placebo in the treatment of knee arthritis.

Ethics approval

The Ethical Review Board of the Paulista School of Medicine – Federal University of Sao Paulo, 08/12/2010, ref: EPM-UNIFESP

Study design

Randomised double-blinded placebo controlled clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

See additional files

Condition

Knee osteoarthritis

Intervention

Interventions section as of 11/01/2017:
Study participants attend a baseline visit at which the following procedures are performed: medical history, physical examination, analysis of X-ray of the affected knee and application of the following questionnaires and tests: Visual Analogue Scale (VAS), Geriatric Pain Measure (GPM), Lequesne’s Index, Timed Up and Go Test (TUG Test), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Short-Form Health Survey (SF-36). Eligible patients are fully informed of the purpose of the study. All patients that fulfill the inclusion criteria signed the informed consent prior to enrolment in the trial. They are instructed to continue their medical treatment according to their physicians’ orientations.

With the objective of avoiding selection bias, all included participants are sequentially assigned by the researchers to receive OZ or PBO according to a pre-established computer-generated global randomization list. This is carried out in such a manner as to guarantee each patient an equal chance of receiving the intervention. The randomization list is generated using software ETCETERA, version 2.46, and constituted 98 numbers with the corresponding treatments. Prior to the beginning of the randomization it has been stipulated that group A would be the ozone group and B, the placebo group.

Ozone group (OZ): Participants receive one intra articular injection of ozone 20 µg/ml (10ml) per week for 8 consecutive weeks.

Placebo group (PBO): Participants receive one intra articular injection of 10 ml of air per week for 8 consecutive weeks.

Assessments are performed at baseline (visit 1), 4 weeks (visit 2), 8 weeks (visit 3), and 8 weeks after the end of the injections (visit 4). At the follow-up visits, the same procedures as those described for visit 1 are performed.

Original interventions section:
Patients will be randomized to receive either intra articular ozone, 20µg/ml once a week for 8 consecutive weeks, or intra articular air, once a week, for 8 consecutive weeks.

The follow-up will last for 2 months after the last session of treatment.

Intervention type

Drug

Phase

Phase III

Drug names

Ozone

Primary outcome measure

Primary outcome measures as of 30/12/2016:
Reduction of pain measured according to
1. Visual Analogue Scale (VAS)
2. Lequesne Algofunctional Index
3. Geriatric Pain Measure (GPM)

All outcomes will be measured at baseline, 4 and 8 weeks and 2 months.

Original primary outcome measures:
Efficacy of treatment measured according to
1. Lequesne Algofunctional Index
2. Time Up and Go Test
3. Activities of Daily Living (ADLs)
4. Medical Outcomes Study 36-Item Short Form
5. Health Survey (MOS SF36 Health Survey)
6. Visual Analogue Scale (VAS)
7. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC Index)

All outcomes will be measured at baseline, 4 and 8 weeks and 2 months.

Secondary outcome measures

Secondary outcome measures as of 30/12/2016:
Improvement of joint function and quality of life according to:
1. Time Up and Go Test
2. Medical Outcomes Study 36-Item Short Form
3. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC Index)

All outcomes will be measured at baseline, 4 and 8 weeks and 2 months

Original secondary outcome measures:
Pain reduction according to
1. Lequesne Algofunctional Index
2. VAS
All outcomes will be measured at baseline, 4 and 8 weeks and 2 months.

Overall trial start date

01/02/2010

Overall trial end date

30/06/2015

Reason abandoned (if study stopped)

Participant inclusion criteria

Inclusion criteria as of 30/12/2016:
1. Patients from Outpatients Department of Geriatrics and Gerontology Discipline – Paulista School of Medicine – Federal University of Sao Paulo, Pro-Vida – Centro de Assistencia Integral a Saude, and Outpatients Department – Rheumatology Discipline – Medical College – Santo Amaro University
2. Aged between 60 years and 85 years
3. Clinically and radiologically confirmed knee osteoarthritis according to the American College of Rheumatology (ACR) criteria

Original inclusion criteria:
1. Patients from Outpatients Department of Geriatrics and Gerontology Discipline da Escola Paulista de Medicina - Universidade Federal de São Paulo
2. Aged more than 60 years or less than 85 years
3. Clinically and radiologically confirmed knee arthritis according to the American College of Rheumatology (ACR) criteria

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

96 patients

Participant exclusion criteria

Exclusion criteria as of 30/12/2016:
1. Patients from Outpatients Department of Geriatrics and Gerontology Discipline – Paulista School of Medicine – Federal University of Sao Paulo, Pro-Vida – Centro de Assistencia Integral a Saude, and Outpatients Department – Rheumatology Discipline – Medical College – Santo Amaro University,
2. Aged between 60 years and 85 years, and
3. Clinically and radiologically confirmed knee osteoarthritis according to the American College of Rheumatology (ACR) criteria.

Original exclusion criteria:
1. Patients aged less than 60 years or more than 75 years
2. Will not give their permission to be included in the study
3. Patients with mental and/or neurologic deficit
4. Diagnosis of secondary osteoarthrosis, patients with recent knee traumas or
5. Suspected associated knee lesion
6. Patients with coxofemoral articulation affections
7. In the acute phase of the disease

Recruitment start date

19/11/2010

Recruitment end date

23/03/2015

Countries of recruitment

Brazil

Trial participating centre

Paulista School of Medicine – Federal University of São Paulo (EPM – UNIFESP)
Outpatients Department – Geriatrics and Gerontology Discipline Rua Prof. Francisco de Castro, 105
São Paulo
04039-001
Brazil

Trial participating centre

Pró-Vida – Center for Total Health Assistance LLC
Av. Paes de Barros, 411 – cj. 14 e 15
São Paulo
03115-020
Brazil

Trial participating centre

University of Santo Amaro – Medicine College
Outpatients Department – Rheumatology Discipline Rua Cássio de Campos Nogueira, 2031
São Paulo
04829-310
Brazil

Organisation

Sao Paolo Medical School (Escola Paulista de Medicina) (Brazil)

Sponsor details

c/o Carlos César Lopes de Jesus
Rua Pedro de Toledo
598
São Paulo
04039-001
Brazil
+55 (0)11 55752970 / 50850248
caceloje@gmail.com

Sponsor type

University/education

Website

Funder type

University/education

Funder name

Sao Paolo Medical School (Escola Paulista de Medicina) (Brazil)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Publication and dissemination plan

Planned publication in a peer reviewed journal.

IPD Sharing plan:
The datasets generated during and/or analysed during the current study will be available upon request from Carlos César Lopes de Jesus (caceloje@gmail.com).

Intention to publish date

31/01/2017

Participant level data

Available on request

Basic results (scientific)

See additional file ISRCTN55861167_BasicResults_11Jan17

Publication list

Publication citations

• ISRCTN55861167_PIS_31Dec16.docx Uploaded 04/01/2017
• ISRCTN55861167_BasicResults_11Jan17.docx Uploaded 12/01/2017

HL 12/01/2017: Results summary uploaded. 11/01/2017: The interventions section has been updated to include further detail of the interventions carried out. 04/12/2016: Participant information sheet uploaded. 03/01/2017: The IPD Sharing plan and plain English summary have been added. 30/12/2016: The following changes have been made to the record: 1. The overall trial dates have been updated from 29/10/2010 - 31/10/2012 to 01/02/2010 - 30/06/2015 and the recruitment dates have been updated from 29/10/2010 - 31/10/2012 to 19/11/2010 - 23/03/2015 2. The target number of participants has been updated from 108 to 96 3. The hypothesis, outcome measures, inclusion criteria and exclusion criteria have been updated 4. The trial participating centres have been added.