search
Back to results

MYPP-trial: Myo-inositol Supplementation to Prevent Pregnancy Complications in Women With Polycystic Ovary Syndrome. (MYPP)

Primary Purpose

Gestational Diabetes Mellitus, Preeclampsia, Preterm Birth

Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Myo-inositol and routinely recommended folic acid
Routinely recommended folic acid
Sponsored by
Erasmus Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Gestational Diabetes Mellitus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • ≥ 18 years of age
  • Diagnosis of PCOS according to the Rotterdam consensus criteria and confirmed by a gynaecologist
  • A viable singleton pregnancy confirmed by ultrasound
  • Being able to initiate the use of study supplements between 8+0 and 16+0 weeks gestational age
  • Ability to understand Dutch or English
  • Ability to provide written informed consent

Exclusion Criteria:

  • Diagnosis of pre-existent type-1 or 2 diabetes mellitus
  • Pre-existent renal failure, defined as an estimated glomerular filtration rate (eGFR) less than 50 ml/min/1.73m2
  • Use of myo-inositol supplements, other insulin-mimetics, hypoglycaemic agents (e.g. metformin) and/or systemic steroids, that cannot be discontinued at the time of inclusion

Sites / Locations

  • Erasmus University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Myo-inositol and routinely recommended folic acid

Routinely recommended folic acid

Arm Description

Myo-inositol is a naturally occurring substance, with a structure quite similar to glucose, which forms an essential component of the cell membrane and is known to support several cellular processes in all living organisms. It is present in nature in high abundance and can be found in many food products. Myo-inositol was historically considered part of the vitamin-B complex and can safely be used as a dietary supplement. In humans, it is synthesized de novo from glucose-6-phosphate in many tissues, mainly in the kidney. Under normal circumstances, the kidneys produce large quantities of myo-inositol, estimated at about 4 grams of endogenous production per day. Myo-inositol has been shown to have a physiological role in supporting the effects of insulin in all living beings. It fulfils a second messenger role in the insulin signalling pathway by enhancing the translocation of GLUT-4 receptors on the plasma membrane and thereby facilitates the intra-cellular uptake of glucose.

Folic acid supplements are part of routine pregnancy care and frequently used as background supplements in previous trials on myo-inositol supplementation in pregnancy.

Outcomes

Primary Outcome Measures

The incidence of PCOS patients in the two study arms that develop Gestational Diabetes Mellitus (GMD).
GDM is defined as any degree of glucose intolerance with onset or first recognition during pregnancy.
The incidence of PCOS patients in the two study arms that develop preeclampsia.
Preeclampsia as defined by the International Society for the Study of Hypertension in Pregnancy (ISSHP).
The incidence of PCOS patients in the two study arm that give birth before 37 completed weeks of gestational age.
Preterm birth is internationally defined as any birth before 37 completed weeks of gestational age.

Secondary Outcome Measures

Maternal mental health assessed by Beck Depression Inventory (BDI) Scale II Netherlands.
The BDI-II-NL measures characteristic attitudes and symptoms of depression and contains 21 items, subdivided in cognitive, affective and somatic factors. Patients rate themselves on these depressive symptoms by endorsing the most relevant statement (ranging in four steps of intensity from minimal to severe) covering a time frame of the past 2 weeks.
Maternal Health Related Quality of Life assessed by 5-Level EuroQol - five dimension (EQ-5D-5L) and Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (PCOSQ)
he EQ-5D-5L records the patient's self-rated health, and a descriptive system. The descriptive system distinguishes five health domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The PCOSQ is the only existing validated, disease-specific, health related quality of life assessment questionnaire. As stated in the new evidence-based PCOS guidelines, this questionnaire could be clinically useful to highlight PCOS features causing greatest distress and was developed to evaluate the effect of treatment in clinical trials in PCOS.
The incidence of neonatal outcomes in the two study arms (e.g. incidence of neonatal intensive care unit (NICU) admissions, incidence of Neonatal hypoglycaemia).
The incidence of Small-for-gestational-age (SGA): babies in the two study arms; birth weight ≤10th percentile or two standard deviations below the mean birth weight for gestational age, using Dutch Perinatal Registry birth weight reference charts. The incidence of Large-for-gestational-age (LGA) babies in the two study arms: birth weight ≥90th percentile for gestational age, using Dutch Perinatal Registry birth weight reference charts. The incidence of NICU admission in the two study arms, including reason for admission and time to discharge or transfer to another unit. The incidence of Neonatal hypoglycaemia in the two study arms:

Full Information

First Posted
July 27, 2022
Last Updated
August 29, 2022
Sponsor
Erasmus Medical Center
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development
search

1. Study Identification

Unique Protocol Identification Number
NCT05524259
Brief Title
MYPP-trial: Myo-inositol Supplementation to Prevent Pregnancy Complications in Women With Polycystic Ovary Syndrome.
Acronym
MYPP
Official Title
MYPP-trial: Myo-inositol Supplementation to Prevent Pregnancy Complications in Women With Polycystic Ovary Syndrome: a Multicentre Double-blind Randomised Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 21, 2019 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. PCOS is a heterogeneous condition, characterised by metabolic disturbances, insulin resistance and hyperandrogenism. Pregnancies in women with PCOS have an increased risk of gestational diabetes mellitus, preeclampsia and preterm birth, and their offspring have an increased risk of aberrant birth weight and hospitalization. After pregnancy, PCOS is thought to have an impact on breastfeeding success and breastmilk composition. Current strategies to improve pregnancy outcome among women with PCOS have not demonstrated significant risk reduction. Myo-inositol is a commonly used dietary supplement with a favourable effect on glucose metabolism and insulin sensitivity. Optimal intake of myo-inositol is associated with a decrease in glucose, lower insulin and lower testosterone levels in women with PCOS. Among women with PCOS-related disorders (e.g. in women with obesity), myo-inositol supplementation in pregnancy has been shown to have clinical benefits in preventing adverse pregnancy outcomes in a number of clinical trials, by reducing the risk of gestational diabetes mellitus, hypertensive complications and preterm birth. The MYPP-trial will be the first randomised prospective trial aimed specifically at pregnant women with PCOS, to evaluate the potential effectiveness of myo-inositol supplementation as a nutritional intervention to prevent all three pregnancy complications associated with PCOS (i.e. GDM, preeclampsia and preterm birth). Secondary objectives are to evaluate the impact of supplementation on maternal (mental) and neonatal health, breastfeeding practices and breastmilk composition. In addition, a full cost-effectiveness analysis will be performed. Women with a diagnosis of PCOS and a singleton pregnancy between 8+0 and 16+0 weeks of gestational age are eligible. Participants randomly allocated to the intervention group will receive 4 grams myo-inositol added to their routinely recommended folic acid supplement, divided over two daily sachets of sugary powder throughout pregnancy. The control group will receive similar looking sachets of supplements containing only the standard dose of folic acid without the added myo-inositol supplement, as part of the current standard-of-care recommendation. In addition to receiving supplements, participants will be asked to complete three questionnaires, provide blood and urine samples once each trimester of pregnancy, and routine ultrasound scanning will be performed to assess fetal growth. All study visits will be aligned with routine antenatal care appointments. Additionally, subjects can choose to participate in research on the impact of myo-inositol supplementation on breastfeeding and take part in the MYPP biobank. The results of this study will provide important novel recommendations for PCOS patients on the importance of optimising life-style and nutrient intake to improve pregnancy outcome.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gestational Diabetes Mellitus, Preeclampsia, Preterm Birth, Polycystic Ovary Syndrome

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
464 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Myo-inositol and routinely recommended folic acid
Arm Type
Active Comparator
Arm Description
Myo-inositol is a naturally occurring substance, with a structure quite similar to glucose, which forms an essential component of the cell membrane and is known to support several cellular processes in all living organisms. It is present in nature in high abundance and can be found in many food products. Myo-inositol was historically considered part of the vitamin-B complex and can safely be used as a dietary supplement. In humans, it is synthesized de novo from glucose-6-phosphate in many tissues, mainly in the kidney. Under normal circumstances, the kidneys produce large quantities of myo-inositol, estimated at about 4 grams of endogenous production per day. Myo-inositol has been shown to have a physiological role in supporting the effects of insulin in all living beings. It fulfils a second messenger role in the insulin signalling pathway by enhancing the translocation of GLUT-4 receptors on the plasma membrane and thereby facilitates the intra-cellular uptake of glucose.
Arm Title
Routinely recommended folic acid
Arm Type
Placebo Comparator
Arm Description
Folic acid supplements are part of routine pregnancy care and frequently used as background supplements in previous trials on myo-inositol supplementation in pregnancy.
Intervention Type
Dietary Supplement
Intervention Name(s)
Myo-inositol and routinely recommended folic acid
Intervention Description
Participants randomly allocated to the intervention group will receive 4 grams myo-inositol added to their routinely recommended 0.4 mg folic acid supplement, divided over two daily sachets of sugary powder throughout pregnancy.
Intervention Type
Dietary Supplement
Intervention Name(s)
Routinely recommended folic acid
Intervention Description
The control group will receive similar looking sachets of supplements containing only the standard dose of 0.4 mg folic acid without the added myo-inositol supplement as part of the current standard-of-care recommendation.
Primary Outcome Measure Information:
Title
The incidence of PCOS patients in the two study arms that develop Gestational Diabetes Mellitus (GMD).
Description
GDM is defined as any degree of glucose intolerance with onset or first recognition during pregnancy.
Time Frame
Measured from 12 weeks up to 28 weeks gestational age using an Oral Glucose Tolerance Test (OGTT)
Title
The incidence of PCOS patients in the two study arms that develop preeclampsia.
Description
Preeclampsia as defined by the International Society for the Study of Hypertension in Pregnancy (ISSHP).
Time Frame
Measured from 20 weeks gestational age up to one week post-partum.
Title
The incidence of PCOS patients in the two study arm that give birth before 37 completed weeks of gestational age.
Description
Preterm birth is internationally defined as any birth before 37 completed weeks of gestational age.
Time Frame
At delivery
Secondary Outcome Measure Information:
Title
Maternal mental health assessed by Beck Depression Inventory (BDI) Scale II Netherlands.
Description
The BDI-II-NL measures characteristic attitudes and symptoms of depression and contains 21 items, subdivided in cognitive, affective and somatic factors. Patients rate themselves on these depressive symptoms by endorsing the most relevant statement (ranging in four steps of intensity from minimal to severe) covering a time frame of the past 2 weeks.
Time Frame
Measured at study inclusion, 36 weeks of pregnancy and 6 weeks postpartum.
Title
Maternal Health Related Quality of Life assessed by 5-Level EuroQol - five dimension (EQ-5D-5L) and Polycystic Ovary Syndrome Health-Related Quality of Life Questionnaire (PCOSQ)
Description
he EQ-5D-5L records the patient's self-rated health, and a descriptive system. The descriptive system distinguishes five health domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The PCOSQ is the only existing validated, disease-specific, health related quality of life assessment questionnaire. As stated in the new evidence-based PCOS guidelines, this questionnaire could be clinically useful to highlight PCOS features causing greatest distress and was developed to evaluate the effect of treatment in clinical trials in PCOS.
Time Frame
Measured at study inclusion, 36 weeks of pregnancy and 6 weeks postpartum.
Title
The incidence of neonatal outcomes in the two study arms (e.g. incidence of neonatal intensive care unit (NICU) admissions, incidence of Neonatal hypoglycaemia).
Description
The incidence of Small-for-gestational-age (SGA): babies in the two study arms; birth weight ≤10th percentile or two standard deviations below the mean birth weight for gestational age, using Dutch Perinatal Registry birth weight reference charts. The incidence of Large-for-gestational-age (LGA) babies in the two study arms: birth weight ≥90th percentile for gestational age, using Dutch Perinatal Registry birth weight reference charts. The incidence of NICU admission in the two study arms, including reason for admission and time to discharge or transfer to another unit. The incidence of Neonatal hypoglycaemia in the two study arms:
Time Frame
Measured form birth and ultimately scored up until six weeks postpartum.
Other Pre-specified Outcome Measures:
Title
Cost-effectiveness of myo-inositol supplementation using Health Technology Assessment (HTA) analyses.
Description
To evaluate the cost-effectiveness of the nutritional intervention from a societal perspective, all resources used in maternity and neonatal care are recorded using questions derived from the Medical Consumption Questionnaire (MCQ).
Time Frame
Measured from study inclusion up until 6 weeks postpartum.
Title
Cost-effectiveness of myo-inositol supplementation using Health Technology Assessment (HTA) analyses.
Description
To evaluate the patient perspective, questions derived from the EQ-5D-5L and the Productivity Cost Questionnaire (PCQ) are incorporated in the study questionnaire
Time Frame
Measured from study inclusion up until 6 weeks postpartum.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥ 18 years of age Diagnosis of PCOS according to the Rotterdam consensus criteria and confirmed by a gynaecologist A viable singleton pregnancy confirmed by ultrasound Being able to initiate the use of study supplements between 8+0 and 16+0 weeks gestational age Ability to understand Dutch or English Ability to provide written informed consent Exclusion Criteria: Diagnosis of pre-existent type-1 or 2 diabetes mellitus Pre-existent renal failure, defined as an estimated glomerular filtration rate (eGFR) less than 50 ml/min/1.73m2 Use of myo-inositol supplements, other insulin-mimetics, hypoglycaemic agents (e.g. metformin) and/or systemic steroids, that cannot be discontinued at the time of inclusion
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rebekka Bout - Rebel, MSc
Phone
31612437377
Email
r.bout-rebel@erasmusmc.nl
Facility Information:
Facility Name
Erasmus University Medical Center
City
Rotterdam
State/Province
South-Holland
ZIP/Postal Code
3015 GD
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rebekka Bout - Rebel, MSc
Phone
31612437377
Email
r.bout-rebel@erasmusmc.nl

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Links:
URL
http://mypp-trial.nl/
Description
Related Info

Learn more about this trial

MYPP-trial: Myo-inositol Supplementation to Prevent Pregnancy Complications in Women With Polycystic Ovary Syndrome.

We'll reach out to this number within 24 hrs