- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04050592
Discontinuation of Postmenopausal Hormone Therapy: Impact on the Cardiovascular System and Quality of Life
Randomized Comparative Trial Between Abrupt and Tapered Discontinuation of Postmenopausal Hormone Therapy: Impact on Endothelial Function, Recurrence of Vasomotor Symptoms and Quality of Life
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Hanna Savolainen-Peltonen, MD, PhD
- Phone Number: +35894711
- Email: hanna.savolainen-peltonen@hus.fi
Study Locations
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-
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Helsinki, Finland, 00290
- Recruiting
- HUS Women's Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- healthy postmenopausal women
- age ≤ 60 years
- has used postmenopausal hormone therapy for at least 3 years
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Group A, Abrupt Discontinuation
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.
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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.
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.
|
Other: Group B, Tapered Discontinuation
Women in group B will discontinue HT (estradiol, 2 mg daily) gradually during study weeks 7-9, as follows:
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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.
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.
|
Active Comparator: Group C, Control Group
Women in Group C, the control group, will continue with HT (estradiol, 2 mg daily) throughout the whole study period of 20 weeks.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
|
8 and 14 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Symptom diary
Time Frame: 5 and 13 weeks
|
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.
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5 and 13 weeks
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Women's Health Questionnaire
Time Frame: 5 and 13 weeks
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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.
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5 and 13 weeks
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Symptom questionnaire
Time Frame: 5 and 13 weeks
|
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.
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5 and 13 weeks
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European Quality of Life Instrument
Time Frame: 5 and 13 weeks
|
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. |
5 and 13 weeks
|
Female Sexual Function Index
Time Frame: 5 and 13 weeks
|
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.
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5 and 13 weeks
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Biomarker: Concentration of endothelin-1
Time Frame: 5 and 8 weeks
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Concentration of endothelin-1 (ET-1, a vasoconstrictive marker, unit pmol/l)
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5 and 8 weeks
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Biomarker: Concentration of nitrite and nitrate
Time Frame: 5 and 8 weeks
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Concentration of nitrite and nitrate (markers of released nitric oxide and consequent vasodilation, unit µmol/l)
|
5 and 8 weeks
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Biomarker: Concentration of Asymmetric Dimethylarginine
Time Frame: 5 and 8 weeks
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Concentration of asymmetric Dimethylarginine (ADMA, inhibitor of NO synthesis and indicator of endothelial dysfunction, unit µmol/l)
|
5 and 8 weeks
|
Biomarker: concentration of sex hormones
Time Frame: 2, 5 and 8 weeks
|
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)
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2, 5 and 8 weeks
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Biomarker: Concentration of coagulation factors
Time Frame: 5 and 8 weeks
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Concentration of coagulation factors: fibrinogen (g/l), plasminogen activator inhibitor-1 (IU/ml), D-dimer (mg/l)
|
5 and 8 weeks
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Biomarker: Concentration of lipids
Time Frame: 5 and 8 weeks
|
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)
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5 and 8 weeks
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Biomarker: Concentration of carbohydrate metabolism
Time Frame: 5 and 8 weeks
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Concentration of carbohydrate metabolism: fasting glucose (mmol/l) and insulin (mU/l)
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5 and 8 weeks
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Biomarker: Concentration of oxidative stress
Time Frame: 5 and 8 weeks
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Concentration of oxidative stress: oxidized LDL (U/l)
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5 and 8 weeks
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Biomarker: Concentration of inflammatory factors
Time Frame: 5 and 8 weeks
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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)
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5 and 8 weeks
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Biomarker: Concentration of advanced glycation end products and soluble form of their receptor
Time Frame: 5 and 8 weeks
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Concentration of advanced glycation end products (AGE, unit U/ml) and soluble form of their receptor (sRAGE, unit pg/ml)
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5 and 8 weeks
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Biomarker: Concentration of cellular adhesion molecules
Time Frame: 5 and 8 weeks
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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)
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5 and 8 weeks
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Concentration of matrix metalloproteinases
Time Frame: 5 and 8 weeks
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Concentration of matrix metalloproteinases (MMPs, unit µM)
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5 and 8 weeks
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Rey Auditory Verbal Learning Test (RAVLT)
Time Frame: 1 and 19 weeks
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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.
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1 and 19 weeks
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Tomi Mikkola, MD, PhD, Helsinki University Central Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- FINNHT1
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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