The Effect of Hydroxytyrosol Administration on Superoxide Dismutase, Pulsatility Index and Resistance Index of Uterine Artery Doppler and Flow-Mediated Dilatation of Brachial Artery In Mothers With Hypertension In Pregnancy (HYDROXY-2)

The Effect of Hydroxytyrosol Administration on Superoxide Dismutase, Pulsatility Index and Resistance Index of Uterine Artery Doppler and Flow-Mediated Dilatation of Brachial Artery In Mothers With Hypertension In Pregnancy: A Randomized Double Blind Controlled Trial

The purpose of this clinical trial is to evaluate the effect of hydroxytyrosol 10 mg/day administered for 4 weeks in pregnant individuals with hypertension. This study will assess whether hydroxytyrosol increases serum superoxide dismutase levels, reduces uterine artery Doppler pulsatility and resistance indices, and improves brachial artery flow-mediated dilation.

Participants will be randomly assigned to receive either hydroxytyrosol or a matching placebo. Both products will be visually identical to ensure blinding. Participants will take two capsules daily for 4 weeks and attend two study visits for assessments and follow-up.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypertension in Pregnancy
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Hydroxytyrosol

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • Jakarta Special Capital Region
    • Jakarta, Jakarta Special Capital Region, Indonesia, 10430
      • Dr. Cipto Mangunkusumo National Central Public Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Singleton pregnancy with a live intrauterine fetus

2. Gestational age 24-32 weeks. Gestational age is confirmed based on:

   • Last Menstrual Period (LMP)
   • First trimester ultrasound biometry

3. Belongs to the Hypertensive Disorders of Pregnancy group, with the following criteria:

   • Gestational hypertension and preeclampsia according to ACOG 2018 criteria
   • Chronic hypertension according to ACOG 2019 criteria
   • Superimposed preeclampsia according to ACOG 2018 criteria

Exclusion Criteria:

1. Pregnancy with infection, including chronic infections such as tuberculosis (TB), HIV, or hepatitis B
2. Pregnancy with other complications (e.g., diabetes mellitus, heart disease, kidney disease, liver disease, malignancy, autoimmune disorders)
3. Refusal to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Group; Participants in this arm will receive a placebo capsule orally twice daily for 4 weeks, alongside standard antenatal care. The placebo is visually identical to the hydroxytyrosol supplement to maintain masking.	Dietary supplement: Placebo; Placebo oral capsule identical in appearance to hydroxytyrosol supplement, administered twice daily for 4 weeks.
Active Comparator: Hydroxytyrosol Group; Participants in this arm will receive hydroxytyrosol 10 mg orally twice daily for 4 weeks, alongside standard antenatal care.	Dietary supplement: Hydroxytyrosol; Hydroxytyrosol is a natural polyphenol with antioxidant and anti-inflammatory properties, derived from olives. In this study, hydroxytyrosol 10 mg will be administered orally twice daily for 4 weeks to assess its effects on blood vessels and inflammatory biomarkers in hypertensive pregnant women.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in superoxide dismutase (SOD) levels measured by colorimetric assay from baseline to week 4.	To evaluate the anti-inflammatory effect of hydroxytyrosol supplementation by comparing the change in superoxide dismutase (SOD) between the hydroxytyrosol and placebo groups after 4 weeks. This examination utilizes blood serum as the test specimen. The reagent kit employed is the Superoxide Dismutase (SOD) Colorimetric Assay Kit (Zellbio GmbH, Germany; Cat: ZX-44108-192, Lot: ZX25003G). Measurements are conducted using a Biorad model 680 Microplate Reader (Bio-rad Laboratories Inc., CA, USA), integrated with Microplate Manager software version 5.2.1 (Bio-rad Laboratories Inc., CA, USA). The sensitivity of the device utilized in this study is 0.044 U/mL.	Baseline and Week 4
Change in Pulsatility Index (PI) of the uterine artery Doppler from baseline to week 4.	To evaluate the anti-inflammatory effect of hydroxytyrosol supplementation by comparing the change Pulsatility Index (PI) of the uterine artery Doppler between the hydroxytyrosol and placebo groups after 4 weeks. All uterine artery doppler examinations are performed using an ultrasound machine (GE Voluson E10, E8, P8, GE Medical Systems, Austria) equipped with a 2-7 MHz convex abdominal probe to obtain the uterine artery flow velocity waveforms. The insonation angle is maintained near 0 degree (<30 degrees), ensuring the peak systolic velocity are greater than 60 cm/second.	Baseline and Week 4
Change in Resistance Index (RI) of the uterine artery Doppler from baseline to week 4.	To evaluate the anti-inflammatory effect of hydroxytyrosol supplementation by comparing the change Resistance Index (RI) of the uterine artery Doppler between the hydroxytyrosol and placebo groups after 4 weeks. All uterine artery doppler examinations are performed using an ultrasound machine (GE Voluson E10, E8, P8, GE Medical Systems, Austria) equipped with a 2-7 MHz convex abdominal probe to obtain the uterine artery flow velocity waveforms. The insonation angle is maintained near 0 degree (<30 degrees), ensuring the peak systolic velocity are greater than 60 cm/second.	Baseline and Week 4
Change in flow-mediated dilation (FMD) of brachial artery measured by an ultrasound from baseline to week 4.	To evaluate the anti-inflammatory effect of hydroxytyrosol supplementation by comparing the change in flow-mediated dilation (FMD) of brachial artery between the hydroxytyrosol and placebo groups after 4 weeks. All FMD of brachial artery examinations are using a GE Voluson P6 ultrasound machine equipped with a 5-13 MHz transducer, and performed by a single operator.	Baseline and Week 4

Collaborators and Investigators

• Sponsor: Dr Cipto Mangunkusumo General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2025
• Primary Completion (Actual): December 31, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: July 24, 2025
• First Submitted That Met QC Criteria: December 9, 2025
• First Posted (Estimated): December 23, 2025

Study Record Updates

• Last Update Posted (Actual): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: hydroxytyrosol
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Hypertension; Hypertension, Pregnancy-Induced; 3,4-dihydroxyphenylethanol
• Other Study ID Numbers: 25-03-0305; Cipto Mangunkusumo Hospital (Other Identifier: Cipto Mangunkusumo Hospital, RSCM Jakarta)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No