The effect of Curcumin, Nigella Sativa, and Curcumin-Nigella Sativa on cellular- molecular and clinical outcomes related to primary osteoporosis among postmenopausal women: A triple blind randomized controlled trial
To determine and comparison of the effect of Curcumin, Nigella Sativa, Curcumin and Nigella Sativa on cellular-molecular and clinical outcomes in postmenopausal women with primary osteoporosis.
Design
In this triple-blind randomized, controlled trial with four parallel arms, 120 postmenopausal women with primary osteoporosis will be randomly assigned into four groups using block randomization with block sizes of 4 and 8, and the ratio of 1: 1: 1: 1, receiving 1) Nigella Sativa, 2) Curcumin nano-missile, 3) Nigella Sativa and Curcumin nano-missile, or 4) both placebo, and will receive the intervention for 6 months.
Settings and conduct
Eligible women will be selected using the information available in Tabriz's health centers, after necessary assessments and receiving written informed consent and will be randomized into one of the four groups, receiving the treatments for six months. Participants, investigators, and statistical analyst will be blinded.
Participants/Inclusion and exclusion criteria
Inclusion criteria: Postmenopausal women aged 50 to 65; Low bone density (T-score <-2.5) in lumbar spine or hip (total and femoral neck)
Exclusion criteria: T-score≤-4 in the lumbar spine, T-score≤-3.5 in the hip and femoral neck; taking drugs affecting bone metabolism; systemic diseases and hormonal disorders; coagulation disorders; gastrointestinal ulcers; gallstone
Intervention groups
Receiving the following daily treatments:
group 1: one 1000 mg Nigella Sativa oil capsule and one Curcumin placebo;
group 2: one 500 mg Curcumin capsule and one Nigella Sativa placebo
group 3: one 500 mg Curcumin capsule and one Nigella Sativa capsule; and
group 4: placebo of the both drugs.
Main outcome variables
Bone mineral density, serum levels of bone turnover markers (osteocalcin, P1NP, BSAP, CTX), and serum levels of some inflammatory and oxidative factors (TAC, SOD, MDA, TNF-α, HS-CRP, IL-6)
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20131009014957N4
Registration date:2018-07-16, 1397/04/25
Registration timing:prospective
Last update:2018-07-16, 1397/04/25
Update count:3
Registration date
2018-07-16, 1397/04/25
Registrant information
Name
Azizeh Farshbaf-khalili
Name of organization / entity
Tabriz university of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 41 1333 9151
Email address
farshbafa@tbzmed.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2018-08-16, 1397/05/25
Expected recruitment end date
2019-12-16, 1398/09/25
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The effect of Curcumin, Nigella Sativa, and Curcumin-Nigella Sativa on cellular- molecular and clinical outcomes related to primary osteoporosis among postmenopausal women: A triple blind randomized controlled trial
Public title
The effect of Curcumin, Nigella Sativa, and Curcumin-Nigella Sativa on outcomes related to primary osteoporosis among postmenopausal women
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Postmenopausal women aged 50 to 65 years
Ability to self-care
Resident of Tabriz city
Menstrual cessation for at least 12 consecutive months
Low bone density (T-score <-2.5) in lumbar spine or hip (total and femoral neck)
No fracture history
The ability to communicate verbally for answering questions
Exclusion criteria:
T-score≤-4 in lumbar spine or T-score≤-3.5 in femoral neck bone
Renal failure and diseases
Bone disease other than osteoporosis
The use of medications that affect bone metabolism, including intravenous bisphosphonate over the past 5 years, oral bisphosphonate use in the last 6 months, cumulative oral bisphosphonate use for more than 3 years, or more than 1 month between 6-12 months before the study, Use of parathyroid hormone analogues over the past 12 months or strontium, fluoride or cathepsin k inhibitor at any time, use of hormonal medications or corticosteroids during the study or within 3 months before (or more).
Chronic liver disease
Other systemic diseases, such as diabetes, gastrointestinal disorders, and endocrine disorders
Mental illness, as reported by the woman
The malignancy, as reported by the woman
Taking anti-coagulants, and coagulation disorders
Stomach ulcers and gallstones
The levels of 25-hydroxyvitamin D less than 20ng/ ml
Current Hypercalcemia or hypocalcemia
Age
From 50 years old to 65 years old
Gender
Female
Phase
3
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data analyser
Data and Safety Monitoring Board
Sample size
Target sample size:
120
Randomization (investigator's opinion)
Randomized
Randomization description
Women with primary osteoporosis were randomly assigned into four groups recieving: 1) Nigella Sativa capsule and curcumin placebo; 2) curcumin capsule and Nigella Sativa placebo; 3) Nigella Sativa and curcumin capsule ; or 4) placebo capsules of Nigella Sativa and curcumin. Allocation sequence will be determined using random blocking of blocks 4 and 8 in RAS software (Random Allocation Software) using a 1: 1: 1: 1 assignment ratio. To conceal the allocation, the medications will be placed inside a consecutively numbered sealed opaque envelopes. Preparation of envelopes and sequence generation will be done by a person not involved in participant recruitment or data collection.
Blinding (investigator's opinion)
Triple blinded
Blinding description
The medications and their placebo will be prepared by the pharmaceutical company in identical shape, color and smell. Investigators, health care providers, outcome assessors, and statistical analyst will be blinded.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Tabriz University of Medical Sciences
Street address
Research Vice-chancellor of Tabriz University of Medical Sciences., End of Gholgasht Ave., Tabriz., Iran
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Approval date
2018-05-14, 1397/02/24
Ethics committee reference number
IR.TBZMED.REC.1397.131
Health conditions studied
1
Description of health condition studied
Postmenopausal osteoporosis
ICD-10 code
M81
ICD-10 code description
Osteoporosis without current pathological fracture
Primary outcomes
1
Description
Bone mineral density
Timepoint
At the baseline (before intervention) and just after completion of the intervention (6 months after beginning the intervention )
Method of measurement
Dual-energy X-ray absorptiometry (DXA)
2
Description
Serum levels of bone turnover markers(osteocalcin، P1NP، BSAP، CTX)
Timepoint
At the baseline (before intervention) and just after completion of the intervention (6 months after beginning of intervention )
Method of measurement
Using the ELISA method
3
Description
Serum levels of some inflammatory factors (TNF-α, HS-CRP, IL-6)
Timepoint
At the baseline (before intervention) and just after completion of the intervention (6 months after beginning of intervention )
Method of measurement
Using calorie meter and ELISA method
Secondary outcomes
1
Description
Frequency of rs2062377 polymorphism of OPG gene
Timepoint
At the baseline (before intervention)
Method of measurement
PCR-RFLP
2
Description
Serum levels of osteoporosis MicroRNA (miR422a، miR-133a، miR-21 و miR-503)
Timepoint
At the baseline (before intervention) and completion of the intervention (6 months after beginning intervention )
Method of measurement
Using the Real-Time PCR method
3
Description
Quality of life score
Timepoint
At the baseline (before intervention) and 1,3, and 6 months after beginning intervention
At the baseline (before intervention) and completion of the intervention (6 months after beginning intervention)
Method of measurement
Body Composition Analyzer
5
Description
The 10-year probability of fracture
Timepoint
At the baseline (before intervention) and completion of intervention (6 months after beginning of study)
Method of measurement
Fracture Risk Assessment Tool (FRAX)
6
Description
Serum levels of some oxidative stress indices (TAC, SOD, MDA)
Timepoint
At the baseline (before intervention) and just after completion of the intervention (6 months after beginning of intervention )
Method of measurement
Using Spectrophotometer and ELISA method
7
Description
Frequency of rs9533090 polymorphism of RANKL gene
Timepoint
At the baseline (before intervention)
Method of measurement
PCR-RFLP
8
Description
Frequency of rs3736228 polymorphism of LRP5 gene
Timepoint
At the baseline (before intervention)
Method of measurement
PCR-RFLP
9
Description
Frequency of rs4869742 polymorphism of ESR1 gene
Timepoint
At the baseline (before intervention)
Method of measurement
PCR-RFLP
10
Description
Frequency of rs6426749 polymorphism of ZBTB40 gene
Timepoint
At the baseline (before intervention)
Method of measurement
PCR-RFLP
Intervention groups
1
Description
Intervention group 1: One Nigella Sativa oil soft-gel capsule 1000 mg once a day prepared by Baryj Essence pharmaceutical company and one Curcumin placebo capsule containing 80 mg carboxymethyl cellulose once a day produced by Exir Nano Sina company, orally by for 6 months,
Category
Treatment - Drugs
2
Description
Intervention group 2: One Curcumin soft-gel capsule containing 80 mg Curcumin as nanomicelle once a day prepared by Exir Nano Sina company, and one Nigella Sativa placebo capsule containing 1000 mg carboxymethyl cellulose once a day produced by Baryj Essence pharmaceutical company, orally for 6 months.
Category
Treatment - Drugs
3
Description
Intervention group 3: One Nigella Sativa oil soft-gel capsule 1000 mg once a day prepared by Baryj Essence pharmaceutical company and one Curcumin soft-gel capsule containing 80 mg Curcumin as nanomicelle once a day prepared by Exir Nano Sina company, orally for 6 months.
Category
Treatment - Drugs
4
Description
Control group: One Nigella Sativa placebo soft-gel capsule containing 1000 mg carboxymethyl cellulose once a day prepared by Baryj Essence pharmaceutical companyand one Curcumin placebo capsule containing 80 mg carboxymethyl cellulose once a day prepared by Exir Nano Sina company, orally for 6 months.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Public health Departments in Tabriz
Full name of responsible person
Dr Mitra Yeghaneh
Street address
Nesfrah Squre., Tabriz health center
City
Tabriz
Province
East Azarbaijan
Postal code
51837
Phone
+98 41 3444 0057
Email
yeghanehm@tbzmed.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Dr. Abolghasem Jouyban
Street address
No. 2 Central building of the university, Golgasht street, Azadi street
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Phone
+98 41 3335 7310
Fax
+98 41 3334 4280
Email
research-vice@tbzmed.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tabriz University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Dr. Azizeh Farshbaf-Khalili
Position
Assistant Professor
Latest degree
Ph.D.
Other areas of specialty/work
Nutrition
Street address
Golgasht Street, Imam Reza Hospital, Ground Floor, Research Center of Physical Medicine and Rehabilitation
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Phone
+98 41 3336 1928
Email
farshbafa@tbzmed.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Dr. Azizeh Farshbaf-Khalili
Position
Assistant Professor
Latest degree
Ph.D.
Other areas of specialty/work
Nutrition
Street address
Golgasht Street, Imam Reza Hospital, Ground Floor, Research Center of Physical Medicine and Rehabilitation
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Phone
+98 41 3336 1928
Email
farshbafa@tbzmed.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Dr. Azizeh Farshbaf-Khalili
Position
Assistant Professor
Latest degree
Ph.D.
Other areas of specialty/work
Nutrition
Street address
Golgasht Street, Imam Reza Hospital, Ground Floor, Research Center of Physical Medicine and Rehabilitation
City
Tabriz
Province
East Azarbaijan
Postal code
5166614766
Phone
+98 41 3336 1928
Email
farshbafa@tbzmed.ac.ir
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
No - There is not a plan to make this available
Statistical Analysis Plan
No - There is not a plan to make this available
Informed Consent Form
No - There is not a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
Title and more details about the data/document
Requested data will be provided to researchers for statistical analysis of the submitted proposal (meta-analysis).
When the data will become available and for how long
starting immediately after publication
To whom data/document is available
Data will be available to researchers as well as to journals.
Under which criteria data/document could be used
The data will be available to researchers upon request and submission of a proposal to perform meta-analysis using IPD data after being unidentified. Also, in exceptional cases, data will be made available to journals for checking.
From where data/document is obtainable
Refer to the email address (farshbafa@tbzmed.ac.ir).
What processes are involved for a request to access data/document
The requests will be sent by email and data will be available within a week.