Trial Title:
The Effectiveness of Astaxanthin Supplementation on the Clinical Symptoms and Cardio-metabolic Profile in Women with Polycystic Ovary Syndrome
NCT ID:
NCT06642363
Condition:
PCO - Polycystic Ovaries
Obesity and Obesity-related Medical Conditions
Conditions: Official terms:
Polycystic Ovary Syndrome
Obesity
Conditions: Keywords:
Astaxanthin
Polycystic Ovary Syndrome
Obesity
Hirsutism
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Masking In this study, the individual conducting the blood test, the one prescribing the
supplements, and the person analyzing the data are unaware of the division of
participants into two groups: drug and placebo. Since the astaxanthin supplement and
placebo are identical in color and shape, patients are also unaware of this division.
Blinding All baseline assessments will be conducted before randomization, and certain
assessments will be performed with blinding for group allocation.
Primary purpose:
Screening
Masking:
Triple (Participant, Care Provider, Investigator)
Masking description:
In this study, the individual conducting the blood test, the one prescribing the
supplements, and the person analyzing the data are unaware of the division of
participants into two groups: drug and placebo. Since the astaxanthin supplement and
placebo are identical in color and shape, patients are also unaware of this division.
Intervention:
Intervention type:
Drug
Intervention name:
Subjects in the intervention group will receive one capsule containing 10 mg Astaper day made by the "Zyest Technology Tarawat Zendig" institute in Iran. The dosage of ASX is determined based on the s
Description:
Subjects in the intervention group will receive one capsule containing 10 mg Astaper day
made by the "Zyest Technology Tarawat Zendig" institute in Iran. The dosage of ASX is
determined based on the s
Arm group label:
Drug
Intervention type:
Drug
Intervention name:
Placebo
Description:
The placebo group will take one capsule containing corn starch in a wrapped and covered
form and the appearance of ASX supplementation (blinding).
Arm group label:
control
Summary:
Abstract Background: This trial aims to investigate the effect of 12 weeks of 10 mg/day
astaxanthin (ASX) administration compared with the control group on insulin sensitivity,
lipid profile, circulating MDA levels, severity of hirsutism, and depression in women
with Polycystic Ovary Syndrome (PCOS).
Methods: This manuscript will outline the design, methodology, and potential clinical
implications of ASX supplementation in eligible women with PCOS and a body mass index of
25-35 kg/m2, who are referred to the gynecologist clinic in Isfahan, Iran, during
2024-2025.
Discussion: This study is one of the first attempts to assess the clinical efficacy of
astaxanthin as an auxiliary treatment in PCOS patients, and will provide more evidence in
this area.
Trial registration number: Iran Clinical Trials (IRCT) website. (IRCT20231001059573N1)
Detailed description:
Introduction Polycystic Ovary Syndrome (PCOS) is a significant endocrine disorder
affecting women of reproductive age, associated with common symptoms, including
anovulation, infertility, metabolic dysfunction, cardiovascular issues, dyslipidemia, as
well as clinical manifestations related to hyperandrogenism. his condition not only leads
to reproductive issues but is also linked to psychological disorders, such as depression.
The exact etiology of PCOS remains incompletely understood; however, it is suggested
that, alongside genetic factors, insulin resistance, an abnormal rise in circulating
testosterone levels, and obesity-related inflammation may contribute to ovarian
dysfunction.
lifestyle intervention is the current recommendation that could enhance anthropometric
indices, cardio-metabolic markers, and reproductive characteristics of women with PCOS.
Recent evidence indicated that the administration of lipid-soluble antioxidants may
influence lipid profiles and lipid peroxidation levels in individuals with PCOS.
Furthermore, previous studies have reported the positive effects of supplementation with
antioxidants on other complications associated with PCOS, including inflammatory markers
and insulin resistance.
Astaxanthin (ASX) is a carotenoid fat-soluble pigment with potential antioxidant
properties naturally found in certain seafood and a specific type of algae. As a
consequence of the unique molecular structure of this component, the beneficial effects
of ASX on various health aspects involving lipid profile, blood pressure, and depression
have been proposed by recent studies . Several experimental investigations also indicated
the anti-oxidative and anti-inflammatory impact of ASX supplementation in various PCOS
models; however, there are limited studies on the impact of ASX on the cardio-metabolic
profile, inflammatory biomarkers, and clinical manifestation of women with PCOS. This
paper will describe the design, methodology, and potential clinical implications of the
impact of ASX supplementation in women with PCOS.
Thus, this trial aims to investigate the effect of 12 weeks of 10 mg/day astaxanthin
administration compared to a control group on insulin sensitivity, lipid profile,
circulating Malondialdehyde (MDA) levels, severity of hirsutism, and depression in women
with PCOS.
Material and methods Study setting and recruitment This is a single-center double-blind,
randomized controlled clinical trial with two parallel groups: one intervention group and
one control group. Eligible women with PCOS who are referred to the collaborating
gynecologist clinic in Isfahan, Iran, in 2024-2025, will be recruited in this study.
After outlining the study's objectives, written informed consent will be obtained from
all participants. All participants will be assigned a project-specific code that will be
used throughout all data analyses.
Randomization and allocation Data on general information and socio-economic status will
be obtained through face-to-face interviews. After recording information at baseline,
participants will be randomly divided into two intervention and placebo groups. Using the
Permuted Block Randomization method and a table of random numbers, patients will be
randomly allocated to receive ASX supplements or placebo after stratifying for age, and
metformin intake.
Subjects in the intervention group will receive one capsule containing 10 mg ASX per day
made by the "Zyest Technology Tarawat Zendig" institute in Iran. The dosage of ASX is
determined based on the safe amount of ASX consumption recorded in the relevant articles.
The placebo group will take one capsule containing corn starch in a wrapped and covered
form and the appearance of ASX supplementation (blinding). The pharmaceutical company
coded both participants in the ASX and placebo groups (codes A and B). The investigators
and participants will remain unaware of the allocation, and the code will be kept
concealed until the study concludes.
To ensure participant adherence, all women are requested to return the supplement packs
at each visit (every two weeks), and the remaining prescribed supplements will be counted
within that timeframe. Additionally, the compliance of study participants will be
monitored daily through social networks. Participants will be instructed not to alter
their common diet and physical activities during the study.
Outcome measures Evaluation of general, demographic, and anthropometric characteristics
Participant's general information including age, history of illness, desired disease
phenotype (diagnosis by a doctor with the phenotype section in the demographic
information questionnaire and smoking will be collected through a general information
questionnaire by interview. The questionnaire will be carefully filled with questions
from the participant and the patient's contact number will also be recorded. Data
collection, including laboratory data, blood pressure, and anthropometric measurements
will be assessed at baseline and 12 weeks (post-intervention). For anthropometric
evaluations, all measurements will be performed according to the method provided by the
World Health Organization. Standing height will be measured using a wall-mounted height
meter (Seca 206, Germany) with an accuracy of 0.1 cm without shoes, heels attached to the
wall knees straight, looking forward and shoulders in a normal position. A weight
measurement of people with minimal clothes and without shoes will be done using a digital
scale with an accuracy of 100 grams. BMI will also be calculated by dividing weight (in
kilograms) by the square of height (in meters).
Dietary intake assessment The individual's dietary intake will be evaluated using a
24-hour dietary recall in the four scenarios (at the baseline, 4-week, 8-week, and the
end of the study) by a trained nutritionist. the reported amounts of each food and drink
consumed will be converted to grams per day using the household guidebook. Diet
information analysis will be done using Nutritionist IV software (First Databank, Hearst
Corp, San Bruno, CA, USA).
Physical Activity Assessment Questionnaire The physical activity evaluation of the
participants will be recorded by the short form of the International Physical Activity
Questionnaire (IPAQ) 4 times (at the baseline, 4-week, 8-week, and the end of the study).
To obtain the overall physical activity score based on MET-minutes/week, the score
obtained from 3 activity categories including walking, moderate physical activity, and
vigorous physical activity will be recorded.
Blood pressure measurement To measure blood pressure, patients were asked to rest for 10
minutes, then the measurement was done using a mercury sphygmomanometer (Riester,
Germany). The blood pressure of each person will be measured twice with a time interval
of 10 minutes, in a sitting position, from the right arm and at the level of the heart.
The average of these two measurements was considered as the patient's blood pressure.
Before taking blood pressure, patients will be asked about smoking or drinking coffee in
the previous 2 hours.
Evaluation of the severity of hirsutism To assess the severity of hirsutism, the amount
of total body hair in nine sits (upper lip, chin, chest, upper and lower abdomen, thigh,
upper and lower back, and upper arm) will be evaluated according to the modified
Ferriman-Gallwey (mFG) scoring system. In this system, each body sit will be visually
scored on a scale of 0 to 4, and the maximum score of each participant could be 16. The
final score of 0 to 3 will be measured as non-hirsutism, 4 to 7 will be considered mild
hirsutism, and 8 Up to 11 and 12 to 16 will reflect moderate hirsutism and severe
hirsutism, respectively. Subjects will be asked to not use any removing hair methods
during the study.
Evaluation of biochemical indicators On days zero (before the start of the intervention)
and day 80 (the end of the intervention), 10 cc of blood is taken from the patient in the
morning and collected in a plastic tube. It is left with 3,600 revolutions for 3-4
minutes and poured into microtubes containing 0.5 ml. The samples are stored in a freezer
at -70°C. To reduce the measurement error, all samplings are done at 8-10 in the morning
and in the fasting state. Blood samples taken from patients at the beginning and end of
the study are centrifuged for 10 minutes at 300 rpm to separate their serum. Serum values
of lipid profile (triglyceride (TG) level, total cholesterol, Low-density lipoprotein
cholesterol (LDL-c), and High-density lipoprotein cholesterol (HDL-c) serum) are measured
by enzymatic colorimetric method. To measure serum cholesterol, cholesteryl ester enzymes
are then added to the solution, and cholesterol oxidase is finally converted into
cholesterol-4-en-3-one H₂O₂ and the cholesterol concentration of the sample is obtained
using the quinoneimine colorimetric marker. Lipase enzyme is used to measure TG, which
converts TG into glycerol and fatty acid. Glycerol turns into glycerol phosphate and
finally dihydroxyacetone phosphate, H₂O₂. using the quinoneimine colorimetric indicator,
the TG concentration of the sample is obtained. To measure LDL, first, all lipoproteins
except Very Low-density lipoprotein cholesterol (VLDL), HDL-c, and chylomicrons are
removed, and with the addition of cholesterol esterase, cholesterol oxidase enzymes, H₂O₂
cholestenone is finally made, and LDL-c concentration is obtained by measuring the color
resulting from the reaction. To evaluate serum HDL-c, firstly, lipoproteins containing
apolipoprotein B such as LDL-c, VLDL, and chylomicron are separated with phosphotungstic
acid, magnesium ion, and using quinonimine colorimetric marker and enzyme method, HDL-c
concentration of the sample is obtained. Serum glucose is converted to glucuronic acid,
H₂O₂ by the activity of glucose oxidase, and the glucose concentration is calculated
using the quinonimine indicator. Fasting insulin is measured by the enzyme immunoassay
method. Monoclonal antibodies are added to the serum to connect to two epitopes of
insulin molecules. After adding buffers, insulin concentration is obtained by measuring
light absorption. The HOMA-IR index is used to calculate insulin resistance. To calculate
the HOMA-IR index, fasting insulin in the U/mlμ scale and fasting glucose in the /l nmol
scale are used: HOMA-IR = fasting insulin (μU/L) x fasting glucose (nmol/L)/22.5. Serum
Malondialdehyde (MDA) values are measured by the TBARS method (Arsam Far Biot Company
kit) and with a spectrophotometer or fluorimeter.
Masking In this study, the individual conducting the blood test, the one prescribing the
supplements, and the person analyzing the data are unaware of the division of
participants into two groups: drug and placebo. Since the astaxanthin supplement and
placebo are identical in color and shape, patients are also unaware of this division.
Blinding All baseline assessments will be conducted before randomization, and certain
assessments will be performed with blinding for group allocation.
Sample size People with polycystic ovary syndrome will be selected by convenience
sampling method. The number of samples will be calculated by considering the first type
error α=0.05 and the second type error β=0.2 (80% power) and using the following formula.
=((Z_(1-α/2)+Z_(1-β) )^2×〖(S〗_1^2+S_2^2))/d^2 Based on the primary outcome considered on
inflammatory factors and by placing the numbers obtained from a study conducted on the
effect of astaxanthin supplementation on Malondialdehyde (MDA) [18], the value of d
significant difference observed in the level (p < 0.05) and equal to 0.884 mmol/liter
will be equal to 17 people in each group, which will be 44 people, including the drop of
25% of people during the study.
Statistical analysis In this study, the quantitative variables will be reported as mean
(standard deviation), and qualitative variables will be reported as number (percentage).
The evaluation of the normality of the distribution of quantitative variables will be
done using the skewness index and the Q-Q plot diagram. Intra-group analyses will be
performed using paired t-tests and between-group analyses will be performed using
intention-to-treat analysis. The distribution of qualitative variables will be compared
between two groups using the chi-square test. SPSS version 22 software will be used to
analyze the data with a significance level of P<0.05.
Discussion The complications caused by this disorder are numerous and in addition to
clinical symptoms related to hyperandrogenism (such as hirsutism, acne, and androgenic
alopecia) and lack of ovulation, metabolic and atherosclerotic complications as well as
an increased risk of complications during pregnancy may be observed in these people.
Although, the treatment strategies available for these patients are quite limited,
currently, hormonal combination drugs are considered the first line of treatment.
However, treatment with hormones may be associated with complications such as increased
risk of cardiovascular diseases and high blood pressure. Currently, one of the things
that can be useful for patients with PCOS is improving people's lifestyle, including
proper dietary interventions and more physical activity, which should be considered in
all affected women.
Astaxanthin (ASX) is a carotenoid pigment and a fat-soluble antioxidant found naturally
in certain seafood, including shrimp and crab, as well as in specific types of algae. ASX
is more active than other carotenoids and, unlike them, converts to vitamin A. due to its
unique molecular structure, it has antioxidant properties 500 times stronger than vitamin
E. Astaxanthin's ability to regulate immunity and systemic inflammation has been
confirmed in many studies. Also, in recent studies, the complementary effects of this
antioxidant have been seen to improve blood pressure, lipid profile levels, and systemic
inflammation .
Based on a study in 2011 by Choi et al., which was conducted on 27 people with BMI above
25 for 12 weeks, it was found that treatment with astaxanthin decreased LDL-c and Apo B,
but no significant changes occurred in other lipid biomarkers. Also, after 12 weeks, the
level of MDA and Isoprostan (ISP) decreased in the intervention group, but the total
antioxidant capacity (TAC) increased in this group. Therefore, in general, astaxanthin
supplementation improved the lipid profile (LDL, Apo B) and oxidative stress. Despite
animal studies of the effect of astaxanthin on PCOS, there have been limited human
studies in this field. After comparing our study with one of these human studies, it was
found that in our study, the patient's lipid profile is one of the important factors and
conditions in PCOS patients, blood sugar indicators, which are very important due to the
discussion of insulin resistance, and depression index. DASS (the effect that hormonal
changes will have on mood) is measured, but none of these factors were measured in the
mentioned study. The duration of the study in this article was 60 days, which seemed to
be less time compared to the 80 days of our study. Because in such intervention studies,
the longer the duration of the intervention, the more valid the results will be. In
another study, only TAC (Total antioxidant capacity) level and activation of the Nrf2
axis were measured in PCOS patients. None of the parameters of blood sugar, lipid
profile, depression level, and other antioxidant capacities (malondialdehyde) were
considered. The duration of the study was 40 days and the dose used was 8 mg. But the
length of our study is 80 days and the dose used is 10 mg. Therefore, it will be better
and more efficient in terms of value and validity. Our study will not measure indicators
such as body mass analysis and other antioxidant capacities. However, this study is one
of the first attempts to assess the clinical efficacy of astaxanthin as an auxiliary
treatment in PCOS patients. It will provide more evidence in this area.
Declarations Ethics approval and consent to participate The Ethics Committee of Isfahan
University of Medical Sciences registered this study. Ethical consent will be obtained
from all subjects. This plan is registered on the Iran Clinical Trials (IRCT) website.
All participants may withdraw their cooperation from this project at any time, also all
participants will be able to request compensation if they suffer harm from the trial. All
information obtained from individuals will remain confidential and used only for research
purposes, and the patient's identity will remain confidential following the law. All
costs related to patient tests, which are outside the periodical tests prescribed by the
attending physician, will be borne by the researchers and the organization supporting the
project, and the results of the tests will be provided to the individuals at the end of
the study. At the end of the study, all the people participating in the research will be
thanked in writing. We will publish the results obtained from the study in the form of
articles in prestigious international journals.
Consent for publication Not applicable Availability of data and materials The datasets
used and/or analyzed during the current study are available from the corresponding author
upon reasonable request.
Competing interests The authors declare that they have no competing interests. Funding
Isfahan University of Medical Sciences Authors' contributions L.S, N.SH-M, Z.H, S.S
Design and analyze data. L.S, M.S, A.A Data collection. M.NJ, N.SH-M major contributor in
writing the manuscript. All authors read and approved the final manuscript.
Acknowledgments Not applicable. Patient and Public Involvement Not applicable.
List of abbreviations
PCOS: Polycystic Ovary Syndrome ASX: Astaxanthin MDA: Malondialdehyde IPAQ: International
Physical Activity Questionnaire LDL-c: Low-density lipoprotein cholesterol
HDL-c: High-density lipoprotein cholesterol
TG: Triglyceride
VLDL: Very Low-density lipoprotein cholesterol
consent form Study Title: The effectiveness of Astaxanthin supplementation on the
clinical symptoms and cardio-metabolic profile in women with Polycystic Ovary Syndrome: A
protocol for a randomized double-blinded, placebo-controlled parallel-group study
Sponsor's Study ID: Isfahan University of Medical Sciences Study Doctor: Nafiseh
Shokri-Mashhadi Email: Nafiseh.shokri@yahoo.com Fax: +9836681378 Postal code: 81746-73461
Sponsor/Funder(s): Isfahan University of Medical Sciences Trial registration number: Iran
Clinical Trials (IRCT) website. (IRCT20231001059573N1) Emergency Contact Number (24 hours
/ 7 days a week): +989171254752 INTRODUCTION You are being invited to participate in a
clinical trial (a type of study that involves research). You are invited to participate
in this trial because you have Study entry conditions. This consent form provides you
with information to help you make an informed choice. Please read this document carefully
and ask any questions you may have. All your questions should be answered to your
satisfaction before you decide whether to participate in this research study.
Please take your time in making your decision. You may find it helpful to discuss it with
your friends and family.
The study staff will tell you about the study timelines for making your decision.
Taking part in this study is voluntary. Deciding not to take part or deciding to leave
the study later will not result in any penalty or affect current or future health care.
IS THERE A CONFLICT OF INTEREST? The authors declare that they have no competing
interests. WHY IS THIS STUDY BEING DONE? This trial aims to investigate the effect of
astaxanthin (ASX) on insulin sensitivity, lipid profile, circulating MDA levels, severity
of hirsutism, and depression in women with Polycystic Ovary Syndrome (PCOS).
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY? It is anticipated that about 44 people will
take part in this study, from research sites located in Isfahan, Iran.
This study should take 3 months complete for every participant. WHAT IS THE STUDY
INTERVENTION? Evaluation of general, demographic, and anthropometric characteristics
Dietary intake assessment Physical Activity Assessment Questionnaire Blood pressure
measurement Evaluation of the severity of hirsutism Evaluation of biochemical indicators)
Blood sampling (
WHAT ARE THE RESPONSIBILITIES OF STUDY PARTICIPANTS?
If you choose to participate in this study, you will be expected to:
Tell the study doctor about your current medical conditions; Tell the study doctor about
all prescription and non-prescription medications and supplements, including vitamins and
herbals, and check with the study doctor before starting, stopping or changing any of
these. This is for your safety as these may interact with the intervention you receive on
this study; Tell the study doctor if you are thinking about participating in another
research study; Return any unused study medication; Return any questionnaires that you
take home to complete; Tell the study doctor if you become pregnant or father a child
while participating on this study; Avoid drinking/eating medicine, supplements ASX
supplement is for you alone, and must not be shared with others.
CAN PARTICIPANTS CHOOSE TO LEAVE THE STUDY? You can choose to end your participation in
this research (called withdrawal) at any time without having to provide a reason. If you
choose to withdraw from the study, you are encouraged to contact the study doctor or
study staff.
You may withdraw your permission to use information that was collected about you for this
study at any time by letting the study doctor know. However, this would also mean that
you withdraw from the study.
CAN PARTICIPATION IN THIS STUDY END EARLY?
The study doctor may stop your participation in the study early, and without your
consent, for reasons such as:
The study intervention does not work for you; You are unable to tolerate the study
intervention; You are unable to complete all required study procedures; New information
shows that the study intervention is no longer in your best interest; The study doctor no
longer feels this is the best option for you; The Sponsor decides to stop the study; The
Regulatory Authority Research Ethics Board withdraws permission for this study to
continue; Your group assignment becomes known to you or others (like the study doctor or
study staff); If you plan to, or become, pregnant If this happens, it may mean that you
would not receive the study intervention for the full period described in this consent
form.
If you are removed from this study, the study doctor will discuss the reasons with you
and plans will be made for your continued care outside of the stu
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age 18 - 45 years
2. Clinical diagnosis of polycystic ovary syndrome
3. Have a body mass index of 25-35 kg/m 2
4. Absence of pregnancy and breastfeeding
5. No intake of medicine
6. Not willing to get pregnant during the study
7. No presence of chronic inflammatory diseases or other endocrine disorders
8. No current treatments except metformin
9. No intake of dietary supplements within at last 2 previous months
Exclusion Criteria:
1. Consuming less than 80% of the total administered ASX supplements
2. Ongoing pregnancy
3. Changing their usual diet or eating habits or level of physical activity
4. Presence of Skin or digestive allergy symptoms or any desired complications by
intake of ASX supplementation
5. Smoking or alcohol consumption
Gender:
Female
Gender based:
Yes
Gender description:
eligible women with PCOS and a body mass index of 25-35 kg/m2, who are referred to the
gynecologist clinic in Isfahan, Iran,
Minimum age:
18 Years
Maximum age:
45 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Isfahan university of medical sciences
Address:
City:
Isfahan
Zip:
8174673461
Country:
Iran, Islamic Republic of
Status:
Recruiting
Contact:
Last name:
Nafiseh Shokri-Mashhadi, Dr
Phone:
+989133311886
Phone ext:
0098
Email:
nafiseh.shokri@yahoo.com
Start date:
July 22, 2024
Completion date:
July 22, 2025
Lead sponsor:
Agency:
Isfahan University of Medical Sciences
Agency class:
Other
Source:
Isfahan University of Medical Sciences
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06642363
