Effect of Monazite Sands in Patients With Osteoarthritis of the Knee
Phase: NA
Conditions: Osteo Arthritis Knee
Sponsor: University Vila Velha

 
 
 
 
Document date: May 2nd , 2019
Official Title: 
Effect of Monazite Sands in Patients with Osteoarthritis 
of the Knee 
Ethical committee Protocol No: 3.160.891  
 
Study protocol 

1. Type of study 
A randomized, blind-control clinical trial with paired samples will be conducted. Patients who 
meet the diagnostic criteria proposed by NICE (2014) with approximately 150 patients who 
agree to participate in the study and sign the Free and Informed Consent Term (Appendix A) 
will be elected. 
2. Experimental Protocol 
The study will be carried out on the beaches of Areia Preta de Guarapari (source of monazitic 
sands) and on the beach of Itapoã in Vila Velha (sand without radiation). Selected patients will 
have their knees fully covered with beach sand, properly analyzed for radioactivity and 
temperature, for 30 minutes on 2 mornings a week for a period of 1 (one) year. 
Patients will be enrolled in relation to age, gender, weight, height and body mass index (BMI). 
An investigation / monitoring will be performed regarding the current use of medications for 
disease control and associated comorbidities. 
3. The size of the sample 
The sample size of the patients was calculated considering the necessary amount of subjects to 
detect difference of at least 3 points in the pain perception through the visual analgesic scale 
(scale from 0 to 10), considering a significance level of 1% and test power of 95% in two-tailed 
hypothesis test, as well as the value of 4 for standard deviation (MATA et al., 2015). The sample 
was calculated in 126 patients and considering a sample loss around 20%, the number of 
subjects was 150, with 75 subjects in each sample (BENAZZI, FIGUEIREDO, BANASSI, 2010). 
4. Ethical issues 
The ethical issues of submission to the Human Research Ethics Committee will be met. 
The team responsible for patient follow-up and data collection will be properly trained and 
composed of specialists from different areas, including an Orthopedist and a Pharmacist, and 
academics from the Medicine, Nursing, Physiotherapy and Pharmacy Courses at Vila Velha 
University. 
5. Inclusion criteria 
Will be included in the study: 
● Patients who meet the NICE (2014) diagnostic criteria for Primary Knee Osteoarthritis. 
● Age between 30 and 95 years. 
 
 
 
 

6. Exclusion Criteria 
Patients with: 
● History of previous knee surgery. 
● History of fracture in the knee region. 
● History of any secondary OA associated with any cystic arthropathy. 
● Any treatment for the knee with methotrexate. 
● History of hemorrhagic disorders. 
● History of any infiltration of the knee during the previous 6 months (eg corticosteroids and 
hyaluronic acid). 
● Morbid obesity. 
● History of severe psychiatric disorders. 
● History of skin cancer. 
 
7. Removal criteria 
Patients will be removed when: 
● Undergoing knee surgery during the course of the research. 
● Subjected to joint infiltration with corticoids or any other type and medication of intra-
articular use. 
● Heat intolerant or other discomfort during exposure to sand. 
 
For evaluation and follow-up of the volunteers will be carried out in parallel a work of 
pharmaceutical attention with monitoring of the use and frequency of medications, especially 
the use of analgesics and / or anti-inflammatories. 
 
8. Recruitment of volunteers 
The volunteers will be recruited at the basic health units of the municipality of Vila Velha for 
internal dissemination and with the assistance of the Community Teaching Service Interaction 
Program (PISEC) of the Medicine Course of the Vila Velha University to disseminate the project 
to pre-formed groups example: HIPERDIA or group of elderly). 
 

9. Intervention 
Patients selected for the study will have their knee (s) affected by OA fully submerged in the 
beach sand 2 (two) times per week for 30 (thirty) minutes each session at the same location and 
at the same time of day. 
The natural gamma ( ) radiation doses of the monazite sands will be monitored in both groups 
through equipment that counts and accumulates the records for the desired time. In addition, 
the radiation measurements 
 will be associated with the atmospheric and climatic 
measurements of each group. An interview with the patients will be performed initially 
(Appendix B), blood collected for analysis and applied to the Visual Analogue Scale (Annex C) 
and WOMAC (Annex D). The questionnaires as well as the blood collection for laboratory 
analysis will be repeated at the beginning of the study (day zero) and after 1, 2, 3, 6, 9 and 12 
months for later analysis and comparison of the data. 
  
10. Values evaluated 
10.1 Primary outcome Measure: 
Change pain perception through the visual analgesic scale of the volunteers (VAS) 
10.2 Secondary Outcome Measures: 
• 
Change total score (0 - 96) the Western Ontario and McMaster Universities 
Osteoarthritis Index (WOMAC)- (lower scores indicate lower levels of symptoms or 
physical disability) 
• 
Reduction of Nonspecific inflammatory markers: evaluation of nonspecific 
inflammatory markers (HSV and CRP) and specific (IL-1β, IL-6, IL-8, IL-17, TNF-α and 
TGF-β) 
• 
Reduction of Self-medication to treat pain 
 
11. Collection of biological material 
Volunteers blood samples will be taken at time zero, after 1, 2, 3, 6, 9 and 12 months, after 
agreement and signature of the ICF. Blood collection will be performed by a specialist in the 
laboratory of clinical analyzes at predetermined dates immediately after exposure of the 
patients to the sand. The samples will be transported in an isothermal box with ice to the Vila 
Velha University laboratory, where they will be immediately frozen at -80ºC until analysis. 
 
 
 
 

12. Biochemical analyzes 
12.1- Non-specific markers 
The biochemical analyzes in the blood collected from the volunteers will be performed in the 
laboratory of clinical analysis to be contracted. The following tests will be performed: 
Hemogram, C-reactive Protein and erythrocyte sedimentation rate. 
12.2- Specific markers 
For the study of osteoarthritis, IL-1β, IL-6, IL-8, IL-17, TNF-α and TGF-β are considered as classic 
biomarkers. These cytokines will be quantified in serum samples obtained from patients by the 
Cytometric Bead Array (CBA) technique (BD Bioscincts Pharmigen, San Diego, CA, USA). The CBA 
assay allows multiple cytokines present in serum, plasma or even culture supernatants to be 
separated and quantified by cytometry using a single fluorophore. Samples after being labeled 
will be read by Flow Cytometry using the BD FacsCalibur cytometer, the results obtained will be 
analyzed by FCAP Array Software V3.0 (BD Bioscinces Pharmigen, San Diego, CA, USA). The 
results obtained after analysis will be expressed in pg / mL. The tests and analyzes will be carried 
out in partnership with the Laboratory of Cellular and Molecular Immunology of the Infectious 
Diseases Nucleus (NDI), located at the Federal University of Espírito Santo (UFES). 
13. Clinical evaluation and follow-up of volunteers 
The clinical evaluation and application of the questionnaires in the patients will be made by an 
expert advised of undergraduate students properly trained for the application of the 
questionnaires and of potential alarm signals. 
13.1 Visual Analog Scale  
It consists of a graduated scale of 0 to 10 with regular intervals where zero means absence of 
pain and 10 is the maximum pain already experienced by the patient. 
13.2 WOMAC  
It consists of a questionnaire for specific assessment of the quality of life of patients with knee 
osteoarthritis. It is divided into three domains pain, stiffness and daily activities from 24 
questions in which the patient has 5 response options (none, little, moderate, intense and very 
intense) and from the answers obtained has a score dividing the by the number of items in each 
of the domains. 
13.3 Pharmaceutical Care  
It consists of evaluating the patients' pharmacological therapy, being able to collect data on 
the health situation, use of medications and dosages administered, as well as adverse 
reactions and possible drug interactions. 
 
 

14. Statistical analysis 
Statistical analysis will be performed in the SPSS program (Statistical Package for the Social 
Sciences, version 13.0). For the analysis, descriptive statistics will be performed, with measures 
of central tendency (mean, median and standard deviation), for variables that follow the normal 
distribution. Qualitative variables will be expressed in frequency and percentage. The difference 
will be analyzed by the chi-square test or Fischer test for the categorical variables and the Mann-
Whitney and Student tests for the resulting variables. A statistically significant difference will be 
considered when p <0.05. 
 
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