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Trial registered on ANZCTR


Registration number
ACTRN12614001201662
Ethics application status
Approved
Date submitted
22/10/2014
Date registered
14/11/2014
Date last updated
8/02/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Safety and cost-effectiveness of Ganoderma lucidum (Reishi mushroom) compared to Ceratonia siliqua in patients with Fibromyalgia: a double-blind, randomised, pilot trial.
Scientific title
Safety and cost-effectiveness of Ganoderma lucidum (Reishi mushroom) compared to Ceratonia siliqua in patients with Fibromyalgia: a double-blind, randomised, pilot trial.
Secondary ID [1] 285466 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fibromyalgia 293240 0
Condition category
Condition code
Musculoskeletal 293509 293509 0 0
Other muscular and skeletal disorders
Alternative and Complementary Medicine 293510 293510 0 0
Herbal remedies
Neurological 293695 293695 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The sample will be divided in two groups by one author that does not participate directly neither in the assessment nor in statistic analyses. The groups will be two: the Ganoderma lucidum (GL) group and the Ceratonia siliqua (CS) group. Patients will know that there are two groups and they can be in any of them, but they will not know the group they belong. Given that, the current trial is a double-blind study, neither the patient nor the researcher will know the group the patient has been assigned.

The GL group will take the micromilled GL. The dose will consist on 6g daily for six weeks. The intakes will consist of 3 grams of GL for two times a day, one intake during or immediately after breakfast and one during or immediately after dinner. The administration will be dissolved in warm water and orally ingested. The GL will be provided by the company “MundoReishi” and will be analyzed by the Chair of Mycology of the University of Valladolid, Spain.

The CS group will receive a daily dose of CS flour, which consist on 6g of powder coming from Carob tree (CS). This substance looks very similar to the micromilled GL. The administration will be exactly the same than the other group.
Intervention code [1] 290396 0
Treatment: Other
Comparator / control treatment
Ganoderma lucidum will be compared to Ceratonia siliqua. Both substances look very similar. The administration will be exactly the same for both groups. Ceratonia siliqua could reduce cholesterol and glucose levels and improve the intestinal function. An antidepressant activity mediated by dopamine and noradrenaline has also been found in mice.
Control group
Active

Outcomes
Primary outcome [1] 293324 0
Health-related quality of life (HRQoL) through four different questionnaires:
a) 15D: It is a generic instrument for measuring HRQoL among adults. It comprises 15 dimensions: mobility, vision, hearing, breathing, sleeping, eating, speech, elimination, usual activities, mental function, discomfort and symptoms, depression, distress, vitality, and sexual activity. The score can be represented as a single utility score, which ranges from 0 (death) to 1 (full health). This score can be used to perform cost-effectiveness analysis.
b) SF-12v2: It is a generic instrument for assessing HRQoL covering physical and mental aspects of health. It is an abbreviated version of the SF-36, which consist in 12 items. It comprises 6 dimensions: physical functioning, role limitations, social functioning, pain, mental health, and vitality. A single utility score, specific of the Spanish population, can be calculated for cost-effectiveness analysis from this questionnaire.
c) EQ-5D-5L: It is a generic utility-based instrument for assessing HRQoL. It comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression; and five levels of severity in each dimension. The current health state of the patients (the health state felt the day of the evaluation) is assessed through a Visual Aanalogue Sscale (VAS) from 0 (worst imaginable health status) to 100 (best imaginable health status).
d)Health Utilities Index Mark 3 (HUI3): It is a generic utility-based instrument for assessing HRQoL. It comprises 8 dimensions.
Timepoint [1] 293324 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.
Primary outcome [2] 293325 0
Functional capacity:
It is a composite primary outcome. In order to perform a complete evaluation of the participants´ functional capacity, the battery from Exercise Looks After You (ELAY) study was selected and other tests from different batteries were added. As result, the following fitness outcomes will be measured:
- Upper body strength: Bi-handgrip strength will be measured by using a grip-strength dynamometer (TKK 5401 Model).
- Upper body flexibility: It will be assessed using the back scratch test.
- Lower body flexibility: It will be measured using the “Chair Sit-and-Reach”.
- Balance and agility: dynamic balance will be measured using the three meter version of the Timed Up-and-Go test (TUG).
- The 30-Second Chair Stand Test.
- Aerobic endurance: It will be measured by using the Six Minutes Walk Test.
- Upper body strength: It will be assessed using the “Arm Curl Test”.
- Velocity: The time needed to walk 10m is recorded in the modificated Brisk Walking Test as a measure of velocity.
- Balance: It will be measured using Biodex Balance System. This device measures, in degrees, the tilt about each axis during static and dynamic conditions and calculates a mediolateral stability index, an anteroposterior stability index, and an overall stability index.
- Trunk endurance: It will be assessed by using the method proposed by Ito, Shirado.
Timepoint [2] 293325 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.
Primary outcome [3] 293504 0
Pain:
Pain perception will be evaluated by a previous trained researcher. It will be measured through the digital palpation of the 18 specified tender points with a pressure of 4kg/cm2 made by an stimulator like Ten FDX (Wagner Instrument). Patients must also fill out a VAS twice a day, where they write the pain that they feel at this moment (when they wake up and when they go to bed).
Timepoint [3] 293504 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.
Secondary outcome [1] 310796 0
Primary outcome.

Impact of fibromyalgia:

Two questionnaires will be utilized to assess the impact of FM. The Fibromyalgia Impact Questionnaire (FIQ) is a 10-item, self-administered instrument that covers three domains: function, overall impact and symptoms. A consensus version for Spanish population was developed by Esteve-Vives, Rivera Redondo.

The FIQ was revised in 2009, originating a new questionnaire called Revised Fibromyalgia Impact Questionnaire (FIQ-R). It has the same three domains but differs in some points. The dimension “function” was reduced from 10 to 9 items and modified. The overall impact domain was completely revised to better reflect the overall impact on functional ability and on the perception of reduced function. Four additional items were added to the dimension “symptoms”: tenderness, memory, balance and environmental sensitivity. The validation of the Spanish version of FIQ-R was developed by Salgueiro, Garcia-Leiva.
Timepoint [1] 310796 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.
Secondary outcome [2] 310797 0
Covariables:
- Sociodemographic variables: gender, age, education level, profession, income level, religiosity, postal code and familiar situation.
- Other diseases.
- Current treatment and therapies, years since diagnosis of FM and years since the first symptoms.
- Current pain “at today”.

All these variables will be assessed by direct interview.
Timepoint [2] 310797 0
Before the treatment
Secondary outcome [3] 311184 0
Sleep quality:
The Spanish version of the Pittsburgh Sleep Quality Index (PSQI) will be utilized to assess the sleep quality and the sleep disorders. Its reliability and validity for Spanish Fibromyalgic patients was developed by Hita-Contreras, Martinez-Lopez.
Timepoint [3] 311184 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.
Secondary outcome [4] 311185 0
Depression:
Depressive symptoms are frequent in Fibromyalgia patients. The Geriatric Depression Scale (GDS) has been used on Fibromyalgia research because it is less focus on somatic symptoms than other depression questionnaires and could therefore be a more accurate assessment of depressive symptoms in Fibromyalgia patients independently of their health complaints.
Timepoint [4] 311185 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.
Secondary outcome [5] 311186 0
Body composition and anthropometric measures:
After measurement of the height, different variables of body composition will be evaluated by using a bioelectrical impedance analysis (Tanita BC-418) that allows segmental body analysis. This devices measure the weight, body mass index, fat mass, muscle mass, total body water and free fat mass. The waist-to-hip ratio will be assessed too.
Timepoint [5] 311186 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.
Secondary outcome [6] 311187 0
Happiness:
It will be assessed by using the General Happiness Scale and the Satisfaction with Life Scale (SWLS). In Spanish adults, the SWLS was validated by Vazquez, Duque.
Timepoint [6] 311187 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.
Secondary outcome [7] 311188 0
Blood parameters: Blood pressure and blood lipids and glucose.

The systolic and diastolic blood pressure will be assessed by a professional nurse in the health care center. Blood main lipids and glucose will be assessed by direct blood analysis on the healthcare center before the treatment starts and six weeks after the treatment. Reagent strips will be used if the analyses cannot be done by the health care system.
Timepoint [7] 311188 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.
Secondary outcome [8] 311191 0
Healthy habits:
The healthy habits questionnaire will be used to assess the healthy habits of the participants. This instrument comprises several dimensions. Due to the aims of the current study, only the dimensions “life habits” and “physical exercise” will be considered.
Timepoint [8] 311191 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.
Secondary outcome [9] 311192 0
Drug treatment costs:
A list of the drugs that they are taking will be asked to the participants. The treatment costs of each participant will be calculated in order to perform cost-effectiveness analysis. In addition, participants will be asked for another kind of therapies, such as physiotherapy, acupuncture, psychological therapy or massages.
Timepoint [9] 311192 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.
Secondary outcome [10] 311193 0
Visits to the health care system:
A list of the visits to hospitals, health care centers or any other place of the health care system will be asked in order to perform cost-effectiveness analysis.
Timepoint [10] 311193 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.
Secondary outcome [11] 311194 0
Work absence:
Self-reported work absence will be assessed. A single question about the number of days that the participants did not go to work because of their FM symptoms in the last six weeks will be asked.
Timepoint [11] 311194 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.
Secondary outcome [12] 311195 0
Falls and fear of falling:
Numbers of falls in the past year, six months and six weeks and visual analogic scale where 0 means "no fear to falling" and 10 means "extreme fear to falling"
Timepoint [12] 311195 0
Before the treatment, six weeks after the intervention started, and three weeks after the end of the intervention.

Eligibility
Key inclusion criteria
1. Be diagnosed with fibromyalgia;
2. Be able to communicate effectively with study staff;
3. Be aged more than 18 years;
4. Give written informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Be pregnant;
2. Change the daily life habits during the six weeks of treatment;
3. Take immunosuppressive;
4. Suffer diabetes;
5. Participating in other studies;
6. Take C vitamin supplementation;
7. Take anticoagulants;
Patients may abandon the trial if some circumstances happen: they withdraw informed consent, the researcher or their general practitioner feel that they should withdraw from the study for reasons of safety and the patient does not comply with the treatment for more than 80% of the dose.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 6400 0
Spain
State/province [1] 6400 0

Funding & Sponsors
Funding source category [1] 290069 0
University
Name [1] 290069 0
Fitness and Quality of Life Lab. (AFYCAV)
Faculty of Sport Sciences
University of Extremadura
Address [1] 290069 0
Avda. de la universidad s/n - 10003 Caceres
Country [1] 290069 0
Spain
Funding source category [2] 290134 0
Commercial sector/Industry
Name [2] 290134 0
MundoReishi will provide the reishi free of charge.
Address [2] 290134 0
Calle Maria de Padilla 6 Bajo B. 34003 - Palencia - Spain

Country [2] 290134 0
Spain
Primary sponsor type
Individual
Name
Francesco Pazzi
Address
Fitness and Quality of Life Lab. (AFYCAV)
Faculty of Sport Sciences
University of Extremadura
Avda. de la universidad s/n - 10003 Caceres
Country
Spain
Secondary sponsor category [1] 288760 0
None
Name [1] 288760 0
Address [1] 288760 0
Country [1] 288760 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291773 0
Comision de Bioetica y de Bioseguridad de la Universidad de Extremadura
Ethics committee address [1] 291773 0
Ethics committee country [1] 291773 0
Spain
Date submitted for ethics approval [1] 291773 0
22/09/2014
Approval date [1] 291773 0
27/10/2014
Ethics approval number [1] 291773 0
91/2014

Summary
Brief summary
Background: Fibromyalgia is characterized by chronic pain and other symptoms like fatigue, reduced health-related quality of life, poor physical functioning, or disrupted sleep.
Ganoderma lucidum has been reported to be safety in humans for reducing pain, fatigue, improves the sleep quality and the health-related quality of life in different populations. Ceratonia siliqua is able to reduce blood cholesterol and glucose, while improving intestinal function and have an antidepressant activity. The present study aims to evaluate the safety and cost-effectiveness of both natural treatments in patients suffering from fibromyalgia.
Methods/design: A double-blind randomized control trial will be developed. A total of 66 patients with fibromyalgia will participate in the study and will be randomly assigned to the Ganoderma lucidum (GL) group” or the Ceratonia siliqua (CS) group. The first group will take 6g daily of Ganoderma lucidum during 6 weeks, while the second group will take the same dose of Ceratonia siliqua flour. A three-week follow-up will be carried out after the end of the treatment.
Discussion: To our knowledge, this is the first study designed to assess the safety and cost-effectiveness of Ganoderma lucidum and Ceratonia siliqua in patients with FM. If our hypothesis were proved, the results of this study would provide a safe, natural and relatively low-cost alternative to treat the FM symptoms.
Trial website
https://sites.google.com/site/fibroreishii
Trial related presentations / publications
Collado-Mateo D., Pazzi F., Dominguez-Muñoz F.J., Martin-Martinez J.P., Olivares P.R., Adsuar J.C., Gusi N. (2015). El Ganoderma lucidum mejora la condición física en mujeres con fibromialgia. Nutrición Hospitalaria 32(5). DOI: http://dx.doi.org/10.3305%2Fnh.2015.32.5.9601
Public notes

Contacts
Principal investigator
Name 51970 0
Mr Francesco Pazzi
Address 51970 0
Fitness and Quality of Life Lab. (AFYCAV)
Faculty of Sport Sciences
University of Extremadura
Avda. de la universidad s/n - 10003 Caceres
Country 51970 0
Spain
Phone 51970 0
+34 635 110 438
Fax 51970 0
Email 51970 0
frapaz76@gmail.com
Contact person for public queries
Name 51971 0
Mr Francesco Pazzi
Address 51971 0
Fitness and Quality of Life Lab. (AFYCAV)
Faculty of Sport Sciences
University of Extremadura
Avda. de la universidad s/n - 10003 Caceres
Country 51971 0
Spain
Phone 51971 0
+34 635 110 438
Fax 51971 0
Email 51971 0
frapaz76@gmail.com
Contact person for scientific queries
Name 51972 0
A/Prof Jose Carmelo Adsuar
Address 51972 0
Fitness and Quality of Life Lab. (AFYCAV)
Faculty of Sport Sciences
University of Extremadura
Avenida de la Universidad s/n - 10003 - Caceres
Country 51972 0
Spain
Phone 51972 0
+34 927 257460
Fax 51972 0
+34 927 257461
Email 51972 0
carmelo.adsuar@gmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary