Protocol summary
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Study aim
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To evaluate the effect of Cinnamon supplementation during controlled ovarian stimulation in patients with polycystic ovary syndrome in a double-blind randomized clinical trial
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Design
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A double-blind randomized controlled phase III clinical trial with parallel groups of 80 patients, in which the Rand function of Excel software will be used for randomization.
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Settings and conduct
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This study will be conducted in Royan Institute on patients with polycystic ovary syndrome undergoing in vitro fertilization cycle treatment. The controlled ovarian stimulation method will be the same in all participants using the standard antagonist protocol. Patients will be randomly assigned into two groups using the block method in a size of 6, and each person will be given an exclusive code to keep the allocation hidden. The details of random allocation in terms of drug and placebo grouping are solely at the disposal of the project's pharmacist colleague, who have no role in the process of sampling and follow-up of patients.
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Participants/Inclusion and exclusion criteria
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All patients diagnosed with polycystic ovary syndrome who are eligible based on the Rotterdam criteria and other inclusion and exclusion criteria stated in the general information section of the clinical trial and who have written consent to participate in the study will be examined.
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Intervention groups
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In the intervention group, women will take 1500 mg daily (3500 mg cinnamon tablets, Sagepad Darou Pharmaceutical Company, Iran) that is, 4 weeks before the start of the new IVF cycle and 2 weeks during the ovarian stimulation process. The method of ovarian stimulation and placebo consumption in the control group will be completely similar to the intervention group.
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Main outcome variables
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Total number of retrieved oocytes; Total number of MII oocytes
General information
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Reason for update
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The update was due to the addition of secondary objectives to the plan.
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20080831001141N44
Registration date:
2023-10-30, 1402/08/08
Registration timing:
prospective
Last update:
2025-01-29, 1403/11/10
Update count:
2
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Registration date
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2023-10-30, 1402/08/08
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2023-11-21, 1402/08/30
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Expected recruitment end date
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2025-11-21, 1404/08/30
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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The effect of cinnamon supplementation on infertility treatment outcomes in infertile women with polycystic ovary syndrome (PCOS) candidate of in vitro-fertilization (IVF): A pilot double blind randomized controlled clinical trial
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Public title
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Investigating the effect of using cinnamon supplements on IVF cycle results in infertile women with polycystic ovary syndrome
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Infertile women with polycystic ovary syndrome (PCOS) diagnosed according to the Rotterdam criteria who meet at least 2 of the following three criteria including: (1) oligomenorrhea or anovulation, (2) hyperandrogenism (clinical or biochemical ng/ dL 80 ≤ serum T level), (3) the presence of polycystic ovaries in ultrasound).
The age range of 18 to 38 year.
Written consent to participate in the study
Exclusion criteria:
Body mass index above 35 kg/m2
Endocrine disorders including diabetes mellitus, hyperprolactinemia, hypertension, Cushing's syndrome
Autoimmune disorders
History of recurrent pregnancy loss
Genital, ovarian or uterine abnormalities
Hydrosalpinx diagnosis
Congenital adrenal hyperplasia, androgen-producing tumors or acromegaly
Sensitivity to cinnamon
Daily and frequent consumption of cinnamon to treat infertility
Severe male factor infertility
Moderate to severe endometriosis diagnosis
Use of other hypoglycemic, insulin-sensitizing drugs (e.g. Metformin) or other antioxidant supplement (e.g. Myo-inositol) and β-blocker before or during the study
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Age
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From 18 years old to 38 years old
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Gender
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Female
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Phase
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3
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Groups that have been masked
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- Participant
- Care provider
- Outcome assessor
- Data analyser
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Sample size
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Target sample size:
80
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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The randomization allocation will be prepared by the methodologist using the Rand function of Excel software. In this method, the blocks in a size of 6 are used and each person will be given an exclusive code in order to hide the allocation. The details of random allocation in terms of drug and placebo grouping are solely at the disposal of the project's pharmacist colleague, who have no role in the process of sampling and follow-up of patients.
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Blinding (investigator's opinion)
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Double blinded
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Blinding description
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The medicine packages, as well as the appearance and smell of cinnamon and placebo tablets, are completely similar to each other. The methodologist prepared the drugs based on the block randomization method and prepared the coded list and put an English three-letter code label on the medicine cans. When an eligible patient is referred to a clinical physician, the principal investigator provides him with an envelope containing a drug code based on a randomized list, and the drug package with the same code is delivered to the patient. In this way, the patient and the clinical doctor following the patient will not know the type of drug (cinnamon or placebo).
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Placebo
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Used
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Assignment
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Parallel
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2023-08-08, 1402/05/17
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Ethics committee reference number
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IR.ACECR.ROYAN.REC.1402.041
Health conditions studied
1
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Description of health condition studied
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Polycystic ovarian syndrome
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ICD-10 code
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E28.2
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ICD-10 code description
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Polycystic ovarian syndrome
Primary outcomes
1
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Description
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Total number of retrieved oocytes
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Timepoint
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Day of oocyte pick-up, 32-34 hours after hCG administration (approximately day 10 of ovarian stimulation)
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Method of measurement
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At the point of ovum pick-up, the total number of retrieved oocytes is counted by the embryologist. Therefore, it will be possible to measure the results one hour after oocytes retrieval.
2
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Description
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Total number of mature (MII) oocytes
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Timepoint
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Day of oocyte pick-up, 32-34 hours after hCG administration (approximately day 10 of ovarian stimulation)
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Method of measurement
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At the point of ovum pick-up, the total number of retrieved oocytes is counted by the embryologist. Therefore, it will be possible to measure the results one hour after oocytes retrieval.
3
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Description
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Oocyte recovery ratio
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Timepoint
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Day of oocyte pick-up, 32-34 hours after hCG administration (approximately day 10 of ovarian stimulation)
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Method of measurement
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This ratio is obtained by dividing the total number of retrieved oocytes by the total number of aspirated follicles from both ovaries.
4
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Description
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Oocyte maturity rate
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Timepoint
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Day of oocyte pick-up, 32-34 hours after hCG administration (approximately day 10 of ovarian stimulation)
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Method of measurement
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This ratio is calculated by dividing the number of mature oocytes (MII) obtained by the total number of retrieved oocytes from both ovaries.
Secondary outcomes
1
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Description
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Fertilization rate
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Timepoint
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17-18 h after intracytoplasmic sperm injection and/or in-vitro insemination by checking the number of polar bodies and pronuclei
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Method of measurement
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The fertilization rate is defined as the ratio between the number of diploid zygotes and the number of mature oocytes.
2
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Description
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Quality of obtained embryos
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Timepoint
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3 days after intracytoplasmic sperm injection or in vitro fertilization (IVF/ICSI) procedure
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Method of measurement
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Embryo grade is assessed under an inverted microscope 3 days after the intracytoplasmic sperm injection procedure. The quality of embryos is graded from 1 to 3 under inverted microscope 3 days after the intracytoplasmic sperm injection procedure. Embryos with even-sized blastomeres and/or ≤10% fragments is classified as Grade 1 (Excellent or good quality). Grade 2 embryos (moderate or fair quality) have blastomeres with slightly-moderate size differences and/or 10- 20% fragments. Grade 3 embryos (poor quality) have markedly different-sized blastomeres and/or >20% fragments.
3
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Description
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PI3K gene expression relative to the housekeeping gene
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Timepoint
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6 weeks after taking cinnamon supplements (oocyte retrieval day)
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Method of measurement
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After collecting follicular fluid on the day of oocyte retrieval, granulosa cells are extracted from the follicular fluid using a density gradient method. RNA is extracted from the cells using a column kit and converted to complementary DNA (cDNA). Then, gene expression is assessed relative to a control gene using real-time PCR
4
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Description
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CYP19A1 gene expression relative to the housekeeping gene
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Timepoint
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6 weeks after taking cinnamon supplements (oocyte retrieval day)
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Method of measurement
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After collecting follicular fluid on the day of oocyte retrieval, granulosa cells are extracted from the follicular fluid using a density gradient method. RNA is extracted from the cells using a column kit and converted to complementary DNA (cDNA). Then, gene expression is assessed relative to a control gene using real-time PCR
5
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Description
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Calpain10 gene expression relative to the housekeeping gene
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Timepoint
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6 weeks after taking cinnamon supplements (oocyte retrieval day)
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Method of measurement
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After collecting follicular fluid on the day of oocyte retrieval, granulosa cells are extracted from the follicular fluid using a density gradient method. RNA is extracted from the cells using a column kit and converted to complementary DNA (cDNA). Then, gene expression is assessed relative to a control gene using real-time PCR
Intervention groups
1
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Description
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Intervention group: patients will take 1500 mg daily (3 tablets of cinnamon 500 mg, Sagepad Darou Pharmaceutical Company, Iran) that is, 4 weeks before the start of the new IVF cycle and 2 weeks during the ovarian stimulation process.
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Category
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Treatment - Drugs
2
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Description
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Control group: patients take 3 placebo pills daily (containing white wheat flour, which is similar to cinnamon pills in terms of size, shape, color and smell, Sagepad Darou Pharmaceutical Company, Iran) 4 weeks before starting the ovarian stimulation/in vitro fertilization (COS/IVF) cycle and 2 weeks during the ovarian stimulation procedure, the ovary will be stimulated.
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Category
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Treatment - Drugs
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Lotus Royan Charitable Fundation
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Proportion provided by this source
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65
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Other
2
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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No
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Title of funding source
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Pharmaceutical grant
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Proportion provided by this source
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35
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Public or private sector
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Private
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Industry
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Yes - There is a plan to make this available
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Study Protocol
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Yes - There is a plan to make this available
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Statistical Analysis Plan
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Not applicable
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Informed Consent Form
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Yes - There is a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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Not applicable
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Data Dictionary
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Not applicable
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Title and more details about the data/document
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The individual data of the participants in the study as well as the data related to the main outcomes of the study without mentioning the names of the patients will be compared and reported between the two groups.
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When the data will become available and for how long
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The access period starts 6 months after the results are published
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To whom data/document is available
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The study data will be available only to researchers working in academic and scientific institutions.
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Under which criteria data/document could be used
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Researchers who intend to write a review and meta-analysis study can access the project data and documentation through correspondence with the project facilitator, whose details are provided on the site
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From where data/document is obtainable
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To access the documents and raw data, it is necessary to study the administrative correspondence with the research deputy of Royan Institute and correspondence with the respondent whose details have been announced on the site.
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What processes are involved for a request to access data/document
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6 months after the publication of the article in scientific journals, they can send their request through official correspondence or email with the research deputy of the Royan Institute. Access to the data may take up to one month after the application is submitted.
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Comments
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