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.
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
- Conditions the study is for
- Menopause, Atherosclerosis, Cardiovascular Diseases
- 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.
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 group | Role | What they receive |
|---|---|---|
| Group A, Abrupt Discontinuation | Other | Women 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 Discontinuation | Other | Women 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 Group | Active comparator | Women 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.
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)
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
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
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
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
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
Biomarker: Concentration of endothelin-1
Concentration of endothelin-1 (ET-1, a vasoconstrictive marker, unit pmol/l)
Measured: 5 and 8 weeks
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
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
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
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
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
Biomarker: Concentration of carbohydrate metabolism
Concentration of carbohydrate metabolism: fasting glucose (mmol/l) and insulin (mU/l)
Measured: 5 and 8 weeks
Biomarker: Concentration of oxidative stress
Concentration of oxidative stress: oxidized LDL (U/l)
Measured: 5 and 8 weeks
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
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
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
Concentration of matrix metalloproteinases
Concentration of matrix metalloproteinases (MMPs, unit µM)
Measured: 5 and 8 weeks
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.
- First posted8 Aug 2019
- Study start19 Feb 2020
- Primary completionDec 2022 (estimated)
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MenopauseStudies 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 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)
Sponsor and investigators
- Lead sponsor
- Hanna Savolainen-Peltonen
- Sponsor type
- University, hospital or other
- Collaborators
- University of Southern California
- Responsible party
- Sponsor-investigator, Hanna Savolainen-Peltonen, Helsinki University Central Hospital
- Investigators
- Tomi Mikkola, MD, PhD, Principal investigator, Helsinki University Central Hospital
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
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04050592
- Acronym / sponsor ID
- FINNHT1
- Keywords
- Randomized Controlled Trial, Menopause, Hormone Therapy, Vasomotor symptoms, Quality of Life, Cardiovascular diseases, Endothelium
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Hanna Savolainen-PeltonenUniversity, hospital or other
- Collaborators
- University of Southern California
- Study start
- 19 Feb 2020 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 8 Aug 2019 (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.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A, Abrupt Discontinuation | Other | Drug: Estradiol, Other: PlaceboWomen 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. |
| Group B, Tapered Discontinuation | Other | Drug: Estradiol, Other: PlaceboWomen 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 |
| Group C, Control Group | Active comparator | Drug: EstradiolWomen in Group C, the control group, will continue with HT (estradiol, 2 mg daily) throughout the whole study period of 20 weeks. |
Who may qualify
- Ages
- Up to 60 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- healthy postmenopausal women
- age ≤ 60 years
- has used postmenopausal hormone therapy for at least 3 years
Key exclusion criteria (6 listed)
- any clinically significant disease
- use of regular medication
- history of cardiovascular events
- history of smoking
- body mass index over 30 kg/m2
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 |
|---|---|---|
| EstradiolActive 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. | Drug | Group A, Abrupt Discontinuation, Group B, Tapered Discontinuation, Group C, Control Group |
| PlaceboThose 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. | Other | Group A, Abrupt Discontinuation, Group B, Tapered Discontinuation |
Primary outcome
Brachial artery flow-mediated dilation (FMD)
Time frame: 8 and 14 weeks
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).
18 secondary outcomes
Symptom diary
Time frame: 5 and 13 weeks
Women's Health Questionnaire
Time frame: 5 and 13 weeks
Symptom questionnaire
Time frame: 5 and 13 weeks
European Quality of Life Instrument
Time frame: 5 and 13 weeks
Female Sexual Function Index
Time frame: 5 and 13 weeks
Biomarker: Concentration of endothelin-1
Time frame: 5 and 8 weeks
Biomarker: Concentration of nitrite and nitrate
Time frame: 5 and 8 weeks
Biomarker: Concentration of Asymmetric Dimethylarginine
Time frame: 5 and 8 weeks
Biomarker: concentration of sex hormones
Time frame: 2, 5 and 8 weeks
Biomarker: Concentration of coagulation factors
Time frame: 5 and 8 weeks
Biomarker: Concentration of lipids
Time frame: 5 and 8 weeks
Biomarker: Concentration of carbohydrate metabolism
Time frame: 5 and 8 weeks
Biomarker: Concentration of oxidative stress
Time frame: 5 and 8 weeks
Biomarker: Concentration of inflammatory factors
Time frame: 5 and 8 weeks
Biomarker: Concentration of advanced glycation end products and soluble form of their receptor
Time frame: 5 and 8 weeks
Biomarker: Concentration of cellular adhesion molecules
Time frame: 5 and 8 weeks
Concentration of matrix metalloproteinases
Time frame: 5 and 8 weeks
Rey Auditory Verbal Learning Test (RAVLT)
Time frame: 1 and 19 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2021.
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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.
Tomi Mikkola, MD, PhD principal investigator
Helsinki University Central Hospital
1 site in 1 country: see every site and its status.
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.