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MenopausePhase 4NCT04050592

Discontinuation of Postmenopausal Hormone Therapy: Impact on the Cardiovascular System and Quality of Life

A Phase 4 study testing Estradiol in people with Menopause and Atherosclerosis, run by Hanna Savolainen-Peltonen at 1 site in Finland.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Although the impact of postmenopausal hormone therapy (HT) on cardiovascular disease risk has been studied in several large randomized trials, little is known about the acute cardiovascular consequences of HT discontinuation. Read more about this study

Who is it for?
Ages Up to 60 years, women onlyHealthy volunteers can take part
What is being tested?
Estradiol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
150 participants
Where
1 siteFinland
Study dates
19 Feb 2020to Dec 2022
Phase
Phase 4
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 Up to 60 years
  • Women only
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • healthy postmenopausal women
  • age ≤ 60 years
  • has used postmenopausal hormone therapy for at least 3 years

Who cannot join

  • any clinically significant disease
  • use of regular medication
  • history of cardiovascular events
  • history of smoking
  • body mass index over 30 kg/m2
  • thickness of endometrium over 6 millimeters

Trial locations and contacts

1 site in 1 country.

Hanna Savolainen-Peltonen, MD, PhD contact

+35894711

hanna.savolainen-peltonen@hus.fi

Finland1 site, 1 recruiting
  • HUS Women's Hospital

    Helsinki, 00290

    Recruiting

Other trials in Finland

About this study

Official title: Randomized Comparative Trial Between Abrupt and Tapered Discontinuation of Postmenopausal Hormone Therapy: Impact on Endothelial Function, Recurrence of Vasomotor Symptoms and Quality of Life

Although the impact of postmenopausal hormone therapy (HT) on cardiovascular disease risk has been studied in several large randomized trials, little is known about the acute cardiovascular consequences of HT discontinuation. In this randomized, double-blind, placebo-controlled trial, the investigators will compare the cardiovascular consequences of abrupt and tapered modes of HT discontinuation in 150 Finnish healthy postmenopausal women under age 60 years. The primary outcome is brachial artery flow-mediated dilatation. In addition, biochemical markers will be measured during the study period of 20 weeks. Health-related quality of life, frequency of hot flush recurrence and other menopausal symptoms will be also assessed in these groups. The trial will provide new high-quality information about the cardiovascular safety as well as the correct timing and method of HT discontinuation.

Being tested
Estradiol, Placebo
Keywords
Randomized Controlled Trial, Menopause, Hormone Therapy, Vasomotor symptoms, Quality of Life, Cardiovascular diseases, Endothelium
Medical subject headings
Atherosclerosis, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EstradiolDrug

    Active intervention is estradiol. Hormone therapy (HT) of all 150 participants will be standardized to 2.0 mg of oral estradiol (E2) without progestogen for six weeks prior to randomization. After that participants will be randomized into three groups (A, B, C) of equal size.

  • PlaceboOther

    Those in groups A and B will switch from estradiol to placebo at the beginning of the 10th week after abrupt or tapered discontinuation of HT.

Study groups in NCT04050592
Study groupRoleWhat they receive
Group A, Abrupt DiscontinuationOtherWomen in group A will discontinue HT (estradiol, 2 mg daily) abruptly after study week 9 and will continue with placebo for study weeks 10-20.
Receives: Drug: Estradiol; Other: Placebo
Group B, Tapered DiscontinuationOtherWomen in group B will discontinue HT (estradiol, 2 mg daily) gradually during study weeks 7-9, as follows: * weeks 7-9: 1 mg estradiol daily for 10 days and then 1 mg estradiol every other day for 11 days. * weeks 10-20: placebo
Receives: Drug: Estradiol; Other: Placebo
Group C, Control GroupActive comparatorWomen in Group C, the control group, will continue with HT (estradiol, 2 mg daily) throughout the whole study period of 20 weeks.
Receives: Drug: Estradiol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Brachial artery flow-mediated dilation (FMD)

    The primary outcome in this study is brachial artery flow-mediated dilation (FMD) to assess endothelial function. To induce reactive hyperemia, a sphygmomanometer cuff is placed on the forearm and inflated to a suprasystolic pressure for five minutes, after which the cuff is deflated. The brachial artery diameter is measured at baseline and during reactive hyperemia, and the relative change in diameter (in millimeters) is calculated. We measure FMD at baseline (at study week 5) and after HT discontinuation (at study weeks 13 and 19).

    Measured: 8 and 14 weeks

Secondary outcomes (18)
  1. Symptom diary

    Participants will keep a symptom diary reporting the exact number, severity and timing of hot flashes during three periods each lasting three weeks: the first period at baseline, the second starting on the 10th week and the third starting on the 18th week. Based on the diary notes, we can assess, how frequent, severe and durable the symptoms are during each period.

    Measured: 5 and 13 weeks

  2. Women's Health Questionnaire

    Women's Health Questionnaire measures emotional and physical health. WHQ includes 37 questions that are answered based on the momentary feeling on a four-point scale (Yes, definitely; Yes, sometimes; No, not so much; No, not at all). The participant receives 37 points at minimum and 148 points at maximum.

    Measured: 5 and 13 weeks

  3. Symptom questionnaire

    The symptom questionnaire includes 19 questions about the frequency of menopausal symptoms (such as hot flashes, night sweats and insomnia) experienced during the past two weeks, and each question is evaluated on a four-point scale (never or seldom; once a month; once a week; almost daily).The participant receives 19 points at minimum and 76 points at maximum.

    Measured: 5 and 13 weeks

  4. European Quality of Life Instrument

    EuroQoL includes a health classification index that covers five dimensions of HRQL (mobility, self-care, usual activities, pain/discomfort, anxiety/depression).The participant receives 5 points at minimum and 15 points at maximum.

    In the second part of the questionnaire, there is a visual analogue scale ranging from 0, "worst imaginable health state", to 100, "best imaginable health state". Thus, the participant receives from 0 to 100 points from this part of the questionnaire.

    Measured: 5 and 13 weeks

  5. Female Sexual Function Index

    This questionnaire includes 19 questions about sexuality. The questions are answered on a five-point scale (almost always or always; most times; sometimes; a few times; almost never or never). The participant receives 19 points at minimum and 95 points at maximum.

    Measured: 5 and 13 weeks

  6. Biomarker: Concentration of endothelin-1

    Concentration of endothelin-1 (ET-1, a vasoconstrictive marker, unit pmol/l)

    Measured: 5 and 8 weeks

  7. Biomarker: Concentration of nitrite and nitrate

    Concentration of nitrite and nitrate (markers of released nitric oxide and consequent vasodilation, unit µmol/l)

    Measured: 5 and 8 weeks

  8. Biomarker: Concentration of Asymmetric Dimethylarginine

    Concentration of asymmetric Dimethylarginine (ADMA, inhibitor of NO synthesis and indicator of endothelial dysfunction, unit µmol/l)

    Measured: 5 and 8 weeks

  9. Biomarker: concentration of sex hormones

    Concentration of sex hormones: Follicle-stimulating hormone (FSH, unit IU/l), luteinizing hormone (LH, unit IU/l), estrone (pmol/l), estradiol (nmol/l) and sex hormone-binding globulin (SHBG, unit nmol/l)

    Measured: 2, 5 and 8 weeks

  10. Biomarker: Concentration of coagulation factors

    Concentration of coagulation factors: fibrinogen (g/l), plasminogen activator inhibitor-1 (IU/ml), D-dimer (mg/l)

    Measured: 5 and 8 weeks

  11. Biomarker: Concentration of lipids

    Concentration of lipids: high-density lipoprotein cholesterol (HDL, unit mmol/l), low-density lipoprotein cholesterol (LDL, unit mmol/l), very low-density lipoprotein cholesterol (VLDL, unit mmol/l), triglycerides (mmol/l) and lipoprotein A (g/l)

    Measured: 5 and 8 weeks

  12. Biomarker: Concentration of carbohydrate metabolism

    Concentration of carbohydrate metabolism: fasting glucose (mmol/l) and insulin (mU/l)

    Measured: 5 and 8 weeks

  13. Biomarker: Concentration of oxidative stress

    Concentration of oxidative stress: oxidized LDL (U/l)

    Measured: 5 and 8 weeks

  14. Biomarker: Concentration of inflammatory factors

    Concentration of interferon-γ (IFN-γ, unit ng/ml), monocyte chemoattractant (MCP-1, unit pg/ml), macrophage inflammatory protein 1α (MIP-1α, unit pg/ml), tumor necrosis factor α (TNF-α, unit pg/ml) and high-sensitivity C-reactive protein (hs-CRP, unit mg/l)

    Measured: 5 and 8 weeks

  15. Biomarker: Concentration of advanced glycation end products and soluble form of their receptor

    Concentration of advanced glycation end products (AGE, unit U/ml) and soluble form of their receptor (sRAGE, unit pg/ml)

    Measured: 5 and 8 weeks

  16. Biomarker: Concentration of cellular adhesion molecules

    Concentration of cellular adhesion molecules: E selectin (mg/dl), intracellular cell-adhesion molecule-1 (ICAM-1, unit ng/ml), vascular cell adhesion molecule-1 (VCAM-1, unit ng/ml)

    Measured: 5 and 8 weeks

  17. Concentration of matrix metalloproteinases

    Concentration of matrix metalloproteinases (MMPs, unit µM)

    Measured: 5 and 8 weeks

  18. Rey Auditory Verbal Learning Test (RAVLT)

    RAVLT evaluates a wide diversity of cognitive functions. Participant is given a list of 15 unrelated words repeated over five different trials and are asked to repeat. Another list of 15 unrelated words are given and the client must again repeat the original list of 15 words and then again after 30 minutes.

    Measured: 1 and 19 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Aug 2019
  2. Study start19 Feb 2020
  3. Primary completionDec 2022 (estimated)
  4. Study completionDec 2022 (estimated)

Resources

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 4
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
150 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04050592
Sponsor's protocol ID
FINNHT1
Status last verified
Feb 2021
First submitted
18 Jun 2019
Last updated
15 Feb 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Estradiol in people with Menopause and Atherosclerosis, run by Hanna Savolainen-Peltonen at 1 site in Finland.

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 3 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 15 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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 Hanna Savolainen-Peltonen, MD, PhD (+35894711, hanna.savolainen-peltonen@hus.fi), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brachial artery flow-mediated dilation (FMD) (time frame: 8 and 14 weeks). 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 15 Feb 2021.

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