Efficacy of intra-articular polynucleotides in the treatment of knee osteoarthritis

ISRCTN	ISRCTN77293496
DOI	https://doi.org/10.1186/ISRCTN77293496
Protocol serial number	plinart 02/06
Sponsor	Mastelli Srl (Italy)
Funder	Mastelli Srl (Italy)

Submission date: 09/04/2009
Registration date: 20/04/2009
Last edited: 20/04/2009

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

Not provided at time of registration

Contact information

Dr Roberto Vanelli
Scientific

IRCCS Foundation
Orthopaedic and Traumatology Department
S. Matteo Hospital Institute
University of Pavia
Viale golgi 19
Pavia
27100
Italy

Study information

Primary study design	Interventional
Study design	Randomised controlled double-blind parallel group clinical trial
Secondary study design	Randomised controlled trial
Scientific title	Efficacy of intra-articular polynucleotides in the treatment of knee osteoarthritis: a controlled, randomised, double-blind clinical trial
Study objectives	The ideal intra-articular treatment for osteoarthritis (OA) should not only provide a mechanical protection of the cartilage surface, but also restore chondrocytes' homeostasis by restoring the physiological articular micro-enivronment and supplying nutrients. Polynucleotides (PN) are polymeric molecules which are able to bind a large amount of water and to re-organise their structure by orienting and co-ordinating water molecules to form a 3-D gel. Polynucleotides when infiltrated at intra-articular level, can deeply moisturise articular surfaces. Polynucleotides, simple nucleotides, nucleosides and nitrogen bases are physiologically present in the extra-cellular environment and are useful substrates for cells. Intra-articular infiltration progressively enriches the synovial fluid of PN and thus of nucleotides, purine and pyrimidine bases that tissues can use to promote physiological repair mechanisms.
Ethics approval(s)	The Ethics Committee of the Clinical Centre (IRCCS Foundation, Orthopaedic and Traumatology Department, S. Matteo Hospital Institute, University of Pavia, Pavia-Italy) approved on the 10th October 2006 (ref: 256)
Health condition(s) or problem(s) studied	Knee osteoarthritis
Intervention	The product under study is a class III medical device, a gel, consisting of highly purified - natural origin long chain polynucleotides (20 mg/ml concentration). It is marked in a pre-filled glass syringe with 2 ml of high molecular weight sterile and apirogenic polynucleotides (batch n° 605553), trade name Turnover Joint and Condrotide (Mastelli Srl, Italy). Control group was treated with hyaluronic acid (HA) in pre-filled glass syringe with 2 ml of 8 mg/ml hyaluronic acid (Sinovial, batch n° 050727, Laboratoires Genévrier, Sophia Antipolis, France). Patients of Group A (treatment group) received five 2 ml intra-articular injections with an interval of one week between the injections (from week 0 to week 4) of 40 mg/2 ml polynucleotides. Group B patients (control group) received five 2 ml intra-articular injections with an interval of one week between the injections (from week 0 to week 4) of 16 mg/2 ml hyaluronic acid.
Intervention type	Drug
Phase	Phase IV
Drug / device / biological / vaccine name(s)	Long chain polynucleotides
Primary outcome measure(s)	Change in the pain level at rest, at weight-bearing, and during physical activity, at all timepoints from baseline (T0) to T16. Timepoints: T0: Inclusion visit T1: After one week T2: After two weeks T3: After three weeks T4: After four weeks (end of treatment period) T8: First follow-up visit, after eight weeks T16: End of the trial, after 16 weeks
Key secondary outcome measure(s)	1. Evaluation of Knee Osteoarthritis Outcome Score (KOOS) results, measured at T0, T4, T8 and T16 2. Non-steroidal anti-inflammatory drug (NSAID) consumption, at all timepoints from baseline (T0) to T16 3. Crackling during movement and articular mobility limitation (LMA), at all timepoints from baseline (T0) to T16 4. Safety profile of the devices, assessed by recording adverse events at each visit Timepoints: T0: Inclusion visit T1: After one week T2: After two weeks T3: After three weeks T4: After four weeks (end of treatment period) T8: First follow-up visit, after eight weeks T16: End of the trial, after 16 weeks
Completion date	20/12/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	60
Key inclusion criteria	1. Aged between 18 and 80 years, either sex 2. Affected by knee osteoarthritis (diagnosis based on the American College of Rheumatology [ACR] classification) 3. Developed persistent pain for at least two months
Key exclusion criteria	1. Alcohol or drug abuse 2. Pregnancy or breastfeeding 3. Hypersensibility to study products 4. Hyaluronic acid or steroid infiltration therapy ongoing or suspended for less than 3 months 5. Systemic treatment with anticoagulants and steroids ongoing or suspended for less than 1 month 6. Previous bone fractures or severe traumas of the interested knee 7. Presence of rheumatoid arthritis and of relevant haematological pathologies
Date of first enrolment	01/12/2006
Date of final enrolment	20/12/2007

Locations

Countries of recruitment

Italy

Study participating centre

IRCCS Foundation

Pavia
27100
Italy

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan