Polycystic Ovarian SyndromeIROP-1NCT03598374
Spontaneous Reproductive Outcomes After Oral Inositol Supplementation in Infertile Polycystic Ovarian Syndrome Women.
A study testing Inositol + Folic acid, Folic acid and Regular intercourses in people with Polycystic Ovarian Syndrome and Infertility, Female, run by Università degli Studi dell'Insubria.
Trial summary
Polycystic ovarian syndrome (PCOS) is a heterogeneous, multifaceted and complex disorder characterized by insulin resistance (IR), hyperinsulinemia, and hyperandrogenism leading ovarian disfunction and infertility. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Polycystic Ovarian Syndrome, Infertility, Female
- What is being tested?
- Inositol + Folic acid, Folic acid and Regular intercourses
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2022to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Women with PCOS diagnosed by Rotterdam criteria in couple that desire to conceive.
Who cannot join
- Male infertility factor that require in vitro fertilization technique.
- Women with infertility factors that require in vitro fertilization technique.
- Couple with infertility factors that require in vitro fertilization technique.
- Diabetes mellitus that require insulin or oral drugs treatment.
- Any other pre-pregnancy or pregnancy-induced/related disease.
- Any other pharmacological, non-pharmacological or nutraceutical treatment (beside oral folic acid supplementation) more than 3 months before the enrollment (wash-out period) or during the trial.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Effects of Oral Inositol Supplementation on Spontaneous Reproductive Outcomes in Infertile Polycystic Ovarian Syndrome Women.
Polycystic ovarian syndrome (PCOS) is a heterogeneous, multifaceted and complex disorder characterized by insulin resistance (IR), hyperinsulinemia, and hyperandrogenism leading ovarian disfunction and infertility. Given the central pathogenic role of IR in the endocrine, reproductive, and metabolic disturbances of PCOS, several pharmacological and non-pharmacological approaches have been proposed to counteract the hyper insulinemic IR typical of the syndrome. Two Inositol stereoisomers, Myo-Inositol (MI) and D-chiro-inositol (DCI), captured the attention of researchers for their insulin-sensitizing actions, which configure them as proper candidates for the treatment of PCOS.
Very few studies reported on spontaneous clinical pregnancy rates, none were powered for this outcome, and none reported on the clinically relevant outcome of live birth. Therefore, data about clinical pregnancy rate, live birth rate, and miscarriage rate comparing inositols with placebo are limited.
Read more
Conversely, about infertility and assisted reproduction techniques (ART), improvements have been reported in PCOS women who underwent fertility treatment using inositol in different forms, combinations or doses. This data, considering the different tissue-specific ratios (i.e., 100:1 in the ovary) and the different physiological roles of inositol stereoisomers, suggest that DCI supplementation alone might not be the optimal or appropriate approach for improving IVF outcomes in PCOS patients, and drawn attention to the importance of MI and DCI supplementation in a physiological ratio in order to restore normal ovary functionality. Indeed, the combination of MI and DCI, at a more physiological ratio of 40:1, was able to more quickly restore to normal the hormonal and metabolic parameters in PCOS women than MI treatment alone or DCI treatment alone, improving the endocrine profile and IR of women with PCOS.
Nevertheless, regarding infertility the primary outcomes that should be considered are clinical pregnancy rate, miscarriage rate and live birth rate. Although many studies showed improved hormonal and metabolic profile and improved ovulation rate and higher quality and number of oocyte retrieved in ART in PCOS women after inositols administration, data about clinical pregnancy rate, live birth rate, and miscarriage rate are limited with several concerns regarding interpretation of the studies.
- Conditions
- Polycystic Ovarian Syndrome, Infertility, Female
- Being tested
- Inositol + Folic acid, Folic acid, Regular intercourses
- Keywords
- Inositol, Polycystic ovarian syndrome, Fertility, Clinical pregnancy rate, Miscarriage rate, Live birth rate
- Medical subject headings
- Polycystic Ovary Syndrome, Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inositol + Folic acidDietary supplement
Daily oral supplementation of for 6 months or until pregnancy conception:
Myo-Inositol: 1100 mg D-chiro-inositol: 27.6 mg Folic acid: 400 mcg
Folic acidDietary supplement
Daily oral supplementation of for 6 months:
Folic acid: 400 mcg
Regular intercoursesBehavioural
Couples are required to have regular intercourses with the aim to achieve a spontaneous conception.
| Study group | Role | What they receive |
|---|---|---|
| Inositol + Folic acid | Experimental | Couples with PCOS infertile women, diagnosed according to the Rotterdam criteria, who access infertility center with conception desire. These women will receive oral supplementation with Inositol (Myo-inositol and D-chiro-inositol at 40:1 ratio) plus Folic acid for 6 months.
Couples are required to have regular intercourse with the aim to achieve a spontaneous conception. Receives: Dietary Supplement: Inositol + Folic acid; Behavioral: Regular intercourses |
| Folic acid | Placebo comparator | Couples with PCOS infertile women, diagnosed according to the Rotterdam criteria, who access infertility center with conception desire. These women will receive oral supplementation with Folic acid for 6 months.
Couples are required to have regular intercourse with the aim to achieve a spontaneous conception. Receives: Dietary Supplement: Folic acid; Behavioral: Regular intercourses |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical pregnancy rate
Number of spontaneous pregnancies conceived per women diagnosed by transvaginal ultrasound. Diagnosis is based on the identification of intrauterine gestational sac with embryo and/or yolk sac.
Measured: Within 6 months from the enrollment
Miscarriage rate
Number of spontaneous abortion per women diagnosed by positive pregnancy test with subsequent spontaneous interruption of the pregnancy.
Measured: Within 6 months from the enrollment
Live birth rate
Number of spontaneous pregnancies per women resulted in a delivered viable fetus.
Measured: Within 18 months from the enrollment
Spontaneous ovulation rate
Spontaneous ovulation activity evaluated by menstrual cycle regularization. Menstrual cycles evaluated by intervals between menstruations (days), day of menstrual blood flow. Rate evaluate considering the number of women with restored regular menstrual cycles per women with irregular menstrual cycles.
Measured: Change in spontaneous ovulation rate, through study completion (an average of 18 months)
Secondary outcomes (5)
Glucose metabolism
OGTT: values of oral glucose tolerance test. Impaired glucose metabolism is diagnosed if fasting glucose values were abnormal (100-125 mg/dl) or glucose tolerance is impaired (2 h plasma glucose within OGTT range of 140-199 mg/dl), and when glucose values exceed threshold values for gestational diabetes (fasting glu- cose value ≥92mg/dl, 1-hour glucose value ≥180mg/dl or 2- hour glucose value ≥153mg/dl)
Measured: Change in glucose metabolism, through study completion (an average of 18 months)
BMI
Body mass index
Measured: Change in BMI, through study completion (an average of 18 months)
Lipid metabolism
Lipid profile assessed by evaluation the high density lipoprotein level and triglycerides level.
Measured: Change in Lipid metabolism, through study completion (an average of 18 months)
Blood pressure
systolic and diastolic blood pressure
Measured: Change in Blood pressure, through study completion (an average of 18 months)
Androgens profile
Serum free testosterone, dehydroepiandrosterone sulfate, and serum SHBG serum concentrations.
Measured: Change in Androgens profile, through study completion (an average of 18 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2018
- Study start1 Jan 2022 (estimated)
- Primary completion30 Jun 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycystic Ovarian SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized multi centre double-blind controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Università degli Studi dell'Insubria
- Sponsor type
- University, hospital or other
- Collaborators
- Universita di Verona
- Responsible party
- Principal investigator, Antonio Simone Laganà, Università degli Studi dell'Insubria
- Investigators
- Antonio Simone Laganà, M.D., Principal investigator, Università degli Studi dell'InsubriaSimone Garzon, M.D., Principal investigator, Universita di VeronaFabio Ghezzi, M.D., Study chair, Università degli Studi dell'InsubriaMassimo Franchi, M.D., Study chair, Universita di Verona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03598374
- Sponsor's protocol ID
- IROP-1
- Acronym
- IROP-1
- Status last verified
- Sep 2021
- First submitted
- 29 Jun 2018
- Last updated
- 30 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Oral Inositol Supplementation on Spontaneous Reproductive Outcomes in Infertile Polycystic Ovarian Syndrome Women.
- ClinicalTrials.gov ID
- NCT03598374
- Acronym / sponsor ID
- IROP-1 / IROP-1
- Conditions
- Polycystic Ovarian Syndrome, Infertility, Female
- Keywords
- Inositol, Polycystic ovarian syndrome, Fertility, Clinical pregnancy rate, Miscarriage rate, Live birth rate
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Università degli Studi dell'InsubriaUniversity, hospital or other
- Collaborators
- Universita di Verona
- Study start
- 1 Jan 2022 (estimated)
- Primary completion
- 30 Jun 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 26 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Polycystic ovarian syndrome (PCOS) is a heterogeneous, multifaceted and complex disorder characterized by insulin resistance (IR), hyperinsulinemia, and hyperandrogenism leading ovarian disfunction and infertility. Given the central pathogenic role of IR in the endocrine, reproductive, and metabolic disturbances of PCOS, several pharmacological and non-pharmacological approaches have been proposed to counteract the hyper insulinemic IR typical of the syndrome. Two Inositol stereoisomers, Myo-Inositol (MI) and D-chiro-inositol (DCI), captured the attention of researchers for their insulin-sensitizing actions, which configure them as proper candidates for the treatment of PCOS.
Very few studies reported on spontaneous clinical pregnancy rates, none were powered for this outcome, and none reported on the clinically relevant outcome of live birth. Therefore, data about clinical pregnancy rate, live birth rate, and miscarriage rate comparing inositols with placebo are limited.
Conversely, about infertility and assisted reproduction techniques (ART), improvements have been reported in PCOS women who underwent fertility treatment using inositol in different forms, combinations or doses. This data, considering the different tissue-specific ratios (i.e., 100:1 in the ovary) and the different physiological roles of inositol stereoisomers, suggest that DCI supplementation alone might not be the optimal or appropriate approach for improving IVF outcomes in PCOS patients, and drawn attention to the importance of MI and DCI supplementation in a physiological ratio in order to restore normal ovary functionality. Indeed, the combination of MI and DCI, at a more physiological ratio of 40:1, was able to more quickly restore to normal the hormonal and metabolic parameters in PCOS women than MI treatment alone or DCI treatment alone, improving the endocrine profile and IR of women with PCOS.
Nevertheless, regarding infertility the primary outcomes that should be considered are clinical pregnancy rate, miscarriage rate and live birth rate. Although many studies showed improved hormonal and metabolic profile and improved ovulation rate and higher quality and number of oocyte retrieved in ART in PCOS women after inositols administration, data about clinical pregnancy rate, live birth rate, and miscarriage rate are limited with several concerns regarding interpretation of the studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized multi centre double-blind controlled trial
| Arm | Type | Receives |
|---|---|---|
| Inositol + Folic acid | Experimental | Dietary Supplement: Inositol + Folic acid, Behavioral: Regular intercoursesCouples with PCOS infertile women, diagnosed according to the Rotterdam criteria, who access infertility center with conception desire. These women will receive oral supplementation with Inositol (Myo-inositol and D-chiro-inositol at 40:1 ratio) plus Folic acid for 6 months. Couples are required to have regular intercourse with the aim to achieve a spontaneous conception. |
| Folic acid | Placebo comparator | Dietary Supplement: Folic acid, Behavioral: Regular intercoursesCouples with PCOS infertile women, diagnosed according to the Rotterdam criteria, who access infertility center with conception desire. These women will receive oral supplementation with Folic acid for 6 months. Couples are required to have regular intercourse with the aim to achieve a spontaneous conception. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Women with PCOS diagnosed by Rotterdam criteria in couple that desire to conceive.
Key exclusion criteria (6 listed)
- Male infertility factor that require in vitro fertilization technique.
- Women with infertility factors that require in vitro fertilization technique.
- Couple with infertility factors that require in vitro fertilization technique.
- Diabetes mellitus that require insulin or oral drugs treatment.
- Any other pre-pregnancy or pregnancy-induced/related disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Inositol + Folic acidDaily oral supplementation of for 6 months or until pregnancy conception: Myo-Inositol: 1100 mg D-chiro-inositol: 27.6 mg Folic acid: 400 mcg | Dietary supplement | Inositol + Folic acid |
| Folic acidDaily oral supplementation of for 6 months: Folic acid: 400 mcg | Dietary supplement | Folic acid |
| Regular intercoursesCouples are required to have regular intercourses with the aim to achieve a spontaneous conception. | Behavioural | Folic acid, Inositol + Folic acid |
Primary outcome
Clinical pregnancy rate
Time frame: Within 6 months from the enrollment
Number of spontaneous pregnancies conceived per women diagnosed by transvaginal ultrasound. Diagnosis is based on the identification of intrauterine gestational sac with embryo and/or yolk sac.
Miscarriage rate
Time frame: Within 6 months from the enrollment
Number of spontaneous abortion per women diagnosed by positive pregnancy test with subsequent spontaneous interruption of the pregnancy.
Live birth rate
Time frame: Within 18 months from the enrollment
Number of spontaneous pregnancies per women resulted in a delivered viable fetus.
Spontaneous ovulation rate
Time frame: Change in spontaneous ovulation rate, through study completion (an average of 18 months)
Spontaneous ovulation activity evaluated by menstrual cycle regularization. Menstrual cycles evaluated by intervals between menstruations (days), day of menstrual blood flow. Rate evaluate considering the number of women with restored regular menstrual cycles per women with irregular menstrual cycles.
5 secondary outcomes
Glucose metabolism
Time frame: Change in glucose metabolism, through study completion (an average of 18 months)
BMI
Time frame: Change in BMI, through study completion (an average of 18 months)
Lipid metabolism
Time frame: Change in Lipid metabolism, through study completion (an average of 18 months)
Blood pressure
Time frame: Change in Blood pressure, through study completion (an average of 18 months)
Androgens profile
Time frame: Change in Androgens profile, through study completion (an average of 18 months)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Simone Laganà, M.D. principal investigator
Università degli Studi dell'Insubria
Simone Garzon, M.D. principal investigator
Universita di Verona
Fabio Ghezzi, M.D. study chair
Università degli Studi dell'Insubria
Questions about this trial
What is this clinical trial studying?
A study testing Inositol + Folic acid, Folic acid and Regular intercourses in people with Polycystic Ovarian Syndrome and Infertility, Female, run by Università degli Studi dell'Insubria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Antonio Simone Laganà, M.D. (+39 329 6279579, antoniosimone.lagana@asst-settelaghi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical pregnancy rate (time frame: Within 6 months from the enrollment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2021.