Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001123336p
Ethics application status
Not yet submitted
Date submitted
15/05/2017
Date registered
31/07/2017
Date last updated
31/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
The Effectiveness of Fatty Tissue for the Treatment of Knee Osteoarthritis
Scientific title
Safety and Efficacy of Autologous Micro-Fragmented Adipose Tissue Injection for the Treatment of Degenerative Knee Osteoarthritis
Secondary ID [1] 291939 0
Sponsor's Protocol No : OA001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteoarthritis 303276 0
Condition category
Condition code
Musculoskeletal 302705 302705 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This procedure will be performed at the minor operation theatre at Aspire Medical Center – Kingdom of Bahrain. Each participant will have his or her own sterile kit that will be used and disposed after the completion of the procedure. Surgical items and instrument is not to be re-used for another procedure. The kit is sterile and the procedure is performed under aseptic technique.
One intravenous cannula will be inserted for the pre-operative analgesia and antibiotic then connected to a normal saline bag to keep the vein open. Thirty minutes before the procedure, a 1g of intravenous Paracetamol and 1g of Ceftriaxone- prophylactic dose of antibiotic intravenously administered to the participant.
During the procedure, only local anesthesia is needed and it will be injected only in the participant’s abdomen- the lipo harvesting site. The participant will be fully awake and aware of what is happening during the procedure while being connected to a nasal cannula for two to four liters of oxygen and monitored via a pulse oximetry.
The orthopedic consultant (the principal investigator (PI)) will perform the procedure solely with the assistance of one scrub nurse and one circulating nurse. In case of any difficulties in lipoaspiration, such as in a case of a very thin participant, a certified plastic surgeon will perform the lipoaspiration only and the remaining steps of the procedure from tissue handling, processing, and intra-articular knee injection will be completed by the PI.
The participant will be lying supine on the theatre bed. They will be exposed from the xiphisternum up to the line drawn between the two anterior superior iliac spines. The harvest site of the procedure is the abdomen. The procedure will take place at both sides of the abdomen. The area will be scrubbed twice with Betadine- an antiseptic solution, and then dried with sterile gauze. Draping of the area will be done using sterile surgical sheets exposing only the area for liposuction.
Procedure steps:
STEP 1 - Harvesting of the adipose tissue
The lower or the lateral abdomen will be chosen as donor site for adipose tissue harvesting. Before harvesting the fat, the site will be injected with Klein solution (1 vial adrenaline + 50 cc lidocaine 2% in 500 cc saline) using a disposable 17G blunt cannula connected to a luer-lock 60-cc syringe. The fat (50 cc) will be then harvested using a 13G blunt cannula, for a fast and a-traumatic suction, connected to a Vaclock"Registered Trademark" 20-ml syringe.
STEP 2 - Processing of the adipose tissue with Lipogems"Registered Trademark" device
The harvested fat will be immediately processed in the Lipogems"Registered Trademark" processing kit, a disposable device that progressively reduces the size of the adipose tissue clusters while eliminating oily substances and blood residues with pro-inflammatory properties. The entire process, carried out in one surgical step, will be performed in complete immersion in physiological solution minimizing any trauma to the cells. The resulting micro-fragmented fat will be collected in a 60-cc syringe and positioned for decanting the excess saline solution. The resulting product will be then transferred into several 1-cc syringes to be injected in the patient.
STEP 3 - Injection in the joint
Micro-fragmented fat (8-10 cc) will be injected to the supralateral angle of patella of each knee. At the end of the procedure, only first aid bandage will be applied to the injection site.
Intervention code [1] 298059 0
Treatment: Other
Comparator / control treatment
No control Group- single group study
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302105 0
The Western Ontario and McMaster Universities Arthritis Index (WOMAC): The WOMAC is a widely used, proprietary set of standardized questionnaires used by healthcare professionals to evaluate the condition of patients with OA of the knee and/or hip. This tools measures pain, stiffness, and physical functioning of the joints. This tool is available in Arabic and English languages, and it will be administered by the investigators (ARHP Research Committee, 2015).
Timepoint [1] 302105 0
Changes from baseline of The Western Ontario and McMaster Universities Arthritis Index (WOMAC) at 1, 3, 6 and 12 months.
Primary outcome [2] 302368 0
Knee Injury and Osteoarthritis Outcome Score (KOOS): KOOS is a comprehensive instrument that is used widely for research purposes in clinical trials. It is developed to subjectively assess the patient’s opinion about their knee and associated problems. KOOS is available in Arabic and English languages and it is self-administered by the patient. It can be used over short and long-term time intervals; to assess changes over weeks or over years. KOOS measures pain, function in daily living activities, function in sports and recreation and knee related Quality of Life (QoL) (Roos, 2016).
Timepoint [2] 302368 0
Changes from baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) at 1, 3, 6 and 12 months.
Primary outcome [3] 302369 0
Visual Analogue Scale (VAS) for pain: the pain VAS is a one-dimensional measure of pain intensity, which has been widely used in diverse adult populations, including those with OA. The VAS is a continuous scale comprised of a 10cm line (100 mm) in length, anchored by 2 verbal descriptors. For pain, the sale is commonly anchored by “no pain” which is “0” on the scale, and “worst pain” which scores “10” on the scale (Hawker, Mian, & Kendzerska, 2011).
Timepoint [3] 302369 0
Changes from baseline at 1, 3, 6 and 12 months.
Secondary outcome [1] 334795 0
Assessment of the knee pain using the Visual Analog Scale (VAS)
Timepoint [1] 334795 0
•Changes from baseline to 12 months post treatment in all assessment scales.
Secondary outcome [2] 336146 0
Blood test for Complete Blood Count (CBC) to rule out anemia
Timepoint [2] 336146 0
•Changes from baseline to 12 months post treatment in all assessment scales.
Secondary outcome [3] 336147 0
white Blood cell count (WBC) to rule out infection
Timepoint [3] 336147 0
•Changes from baseline to 12 months post treatment in all assessment scales.
Secondary outcome [4] 336148 0
X-ray of bilateral knees in two views anteroposterior and lateral and graded by Kellgren-Lawrence scale
Timepoint [4] 336148 0
•Changes from baseline to 12 months post treatment in all assessment scales.
Secondary outcome [5] 336149 0
MRI of both knees will be conducted and graded using BLOCKS scoring system
Timepoint [5] 336149 0
Changes from baseline to 12 months post treatment in all assessment scales.
Secondary outcome [6] 336150 0
The routine measurement of Vital Signs, including: temperature, Blood pressure and Body weight (A Composite Secondary Outcome)
Timepoint [6] 336150 0
Changes from baseline to 12 months post treatment in all assessment scales.
Secondary outcome [7] 337248 0
platelets count to ensure absence of coagulopathy or bleeding tendency
Timepoint [7] 337248 0
Changes from baseline to 12 months post treatment in all assessment scales.

Eligibility
Key inclusion criteria
1. Participant agreeing and able to give informed consent.
2. Symptomatic osteoarthritis of the knee (Grades II and III based on Kellgren and Lawrence system).
3. Age between 18 and 70 years.
4. Participants with body mass index (BMI) up to 35 kg/m2.
5. Failure of conservative treatments for at least 6 months.
6. No surgery for the same indication within 12 months prior to treatment.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants younger than 18 years and older than 70 years.
2. Participants with BMI more than 35 kg/m2.
3. Participants whom underwent bilateral total knee replacement.
4. Bedridden patients.
5. Knee osteoarthritis with the following conditions: complex ligamentous knee joint instability, skeletal immaturity, and osteochondral tumor.
6. Axial malalignment (> 10/15 degrees of varus or valgus).
7. Existing infection in or around the joint.
8. Patients with inflammatory joint disease, autoimmune disease.
9. Patients allergic to Paracetamol.
10. Patients with contraindication to MRI.
11. Vulnerable population (pregnant women, prisoners, military, homeless, elderly, mentally disordered patients, emergency patients).

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
As an exploratory non-randomized single-arm study, the statistical approaches will be largely descriptive in intent.
Since this study is exploratory, a liberal procedure of testing both primary endpoints at two-sided alpha of 5% will be used, and the proposed sample size of 32-40 patients will provide 80% power to detect a change in mean score with effect size 0.5.
Statistical Analysis
Patient Characteristics
A CONSORT-type diagram will be presented showing:
*Numbers screened, with reasons for ineligibility or refusal, where available
*Numbers completing each stage of the study, with reasons for withdrawal or non-compliance with assessments, where available
Demographic data, vital signs at each visit and efficacy assessments at each visit will be presented in summary tables. Discrete data will be summarized by frequency counts, continuous data by mean, SD, media, quartiles and range.
Primary Efficacy Endpoint
The primary analyses will be done by ANCOVA, testing the null hypothesis that the mean change from baseline is zero, conditional on the baseline value. Data will be assumed to be Normally distributed. The point estimates of mean change and associated 95% CIs will be presented.
Primary Safety Endpoints
* AEs will be tabulated by preferred term and by body system. The maximum-recorded grade per patient of each AE will be displayed in these tables.
* CBC data will be listed, and clinically significant values displayed.
* Any Vital Signs data of clinical significance will be displayed.
Secondary Efficacy Endpoints
The effects of treatment on other scales at 12 months will be assessed as for the primary endpoint. In order to assess the effect of treatment at 12 months, while allowing for the possibility of dropouts, mixed effect models with a random patient effect will be fitted to the changes at 3 and 6 months, using time-point and baseline value as fixed effects. Effects and 95% CIs will be presented. In addition daily average paracetamol usage during the trial will be summarized, and a point estimate and 95% CI presented for the mean value. Finally, changes in MRI will be summarized and thoroughly explained.
Exploratory analyses
To inform future work, residuals from all models will be examined for evidence of skewness or heteroscedasticity. If such is found the impact of appropriate variance-stabilizing transformations will be investigated.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
14/08/2017
Actual
Date of last participant enrolment
Anticipated
2/11/2017
Actual
Date of last data collection
Anticipated
29/11/2018
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment outside Australia
Country [1] 8900 0
Bahrain
State/province [1] 8900 0

Funding & Sponsors
Funding source category [1] 296451 0
Self funded/Unfunded
Name [1] 296451 0
Bashar Al Sayed
Country [1] 296451 0
Bahrain
Funding source category [2] 296684 0
Commercial sector/Industry
Name [2] 296684 0
Lipogems Technology
Country [2] 296684 0
Italy
Primary sponsor type
Other
Name
Aspire Medical Center
Address
Road 5804,
Bldg 324
block 358,
Zinj,
Country
Bahrain
Secondary sponsor category [1] 295403 0
Individual
Name [1] 295403 0
Silvia Versari
Address [1] 295403 0
Lipogems International Spa
Viale Bianca Maria 24
20129 Milano MI
Country [1] 295403 0
Italy

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 297676 0
Ethical Committee for Private Practice at NHRA
Ethics committee address [1] 297676 0
National Health Regulatory Authority
Building no. 2420 , Road no. 2831, Block no. 428
Al-Seef District
P.O. Box 11464
Manama
Ethics committee country [1] 297676 0
Bahrain
Date submitted for ethics approval [1] 297676 0
14/08/2017
Approval date [1] 297676 0
Ethics approval number [1] 297676 0

Summary
Brief summary
Over the past two decades, obesity has morbidly increased in an alarming rate in the Gulf countries among adults and children. According to the World Health Organization (WHO), Kuwait, Bahrain, Saudi Arabia and United Arab Emirates are in the list of top ten countries worldwide in terms of obesity (ALNohair, 2014).
Moreover, obesity is considered one of the greatest modifiable risk factor for OA. Obesity is strongly correlated with the incidence and progression of OA of both weight bearing and non-weight bearing joints. It increases the load of the weight-bearing joint, which may be the most important mechanical contribution. Therefore, over-weight can significantly improve the pain level and function of the knees for obese people with OA (King, March, & Anandacoomarasamy, 2013).
Articular cartilage forms the bearing surfaces of all synovial joints. Human articular cartilage has a very limited repair potential which has always imposed a great challenge to orthopedic surgeons.
Replacement by metal prostheses is reserved as a last resort given the finite durability of prostheses as well as the increasing life span and activity levels of the general population. While the outcomes of joint replacement for degenerative joint disease are often favorable, an increased incidence of prosthesis failure over time limits the use of this treatment modality for younger patients -especially highly active ones- for whom a desirable treatment would be the resurfacing of the joint with a biological tissue.
The chondral lesion of the knee represents a challenge for the orthopedic surgeon because of the limited regenerative properties of the affected tissue. A variety of treatments have been proposed (autologous graft, micro-fractures, physical stimulation, biomaterials, etc.) with variable success rates.
Therefore, the availability of a minimally manipulated, autologous adipose tissue would have remarkable biomedical and clinical relevance. The proposed procedure is gentle and intra-operatively provides micro-fragmented adipose tissue in a short time (15-20 minutes), without expansion and/or enzymatic treatment, very rich in mature pericytes and which has been shown to be effective in the treatment of different pathologies.
In this study, the aim of this study is to test if autologous, micro-fragmented and minimally manipulated adipose tissue can provide support and/or significant decrease pain in people with osteoarthritis of the knees.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74782 0
Dr Bashara Al Sayed
Address 74782 0
Aspire Medical Center
Road 5804,
Bldg 324
block 358,
Zinj
Country 74782 0
Bahrain
Phone 74782 0
+97339331533
Fax 74782 0
Email 74782 0
basharalsayed@gmail.com
Contact person for public queries
Name 74783 0
Hayat Mushcab
Address 74783 0
Johns Hopkins Aramco Healthcare
Room 2
Bldg 5816
Dhahran 34465
Country 74783 0
Saudi Arabia
Phone 74783 0
+97338147715
Fax 74783 0
Email 74783 0
hayat.mushcab@gmail.com
Contact person for scientific queries
Name 74784 0
Lama Al Mushkab
Address 74784 0
Aspire Medical Center
Road 5804,
Bldg 324
block 358,
Zinj
Country 74784 0
Bahrain
Phone 74784 0
+97336159915
Fax 74784 0
Email 74784 0
lamaalmushkab@gmail.com

No information has been provided regarding IPD availability


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Results publications and other study-related documents

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