E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
We will assess the effects of hormone therapy termination on endothelial function using biophysical (flow-mediated dilation, peripheral artery tonometry) and biochemical markers. We will compare these effects between healthy postmenopausal women who discontinue long-term HT either abruptly or gradually within four weeks. Finally, we will compare menopausal symptom recurrence and the success rate of HT discontinuation between these two treatment groups.
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E.1.1.1 | Medical condition in easily understood language |
We will asses the effect of hormone therapy discontinuation on endothelial function and menopausal symptom (i.e. hot flush) recurrence in healthy postmenopausal women. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027311 |
E.1.2 | Term | Menopause flushing |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10076936 |
E.1.2 | Term | Impaired quality of life |
E.1.2 | System Organ Class | 10041244 - Social circumstances |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027301 |
E.1.2 | Term | Menopausal hot flushes |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060858 |
E.1.2 | Term | Cardiovascular function test |
E.1.2 | System Organ Class | 10022891 - Investigations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027308 |
E.1.2 | Term | Menopause |
E.1.2 | System Organ Class | 10041244 - Social circumstances |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10027309 |
E.1.2 | Term | Menopause and related conditions |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007649 |
E.1.2 | Term | Cardiovascular disorder |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051775 |
E.1.2 | Term | Postmenopause |
E.1.2 | System Organ Class | 10041244 - Social circumstances |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048554 |
E.1.2 | Term | Endothelial dysfunction |
E.1.2 | System Organ Class | 10047065 - Vascular disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effects of hormone therapy (HT) termination on endothelial function by using biophysical and biochemical markers, and to compare these effects between women who discontinue long-term HT either abruptly or gradually
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E.2.2 | Secondary objectives of the trial |
Compare menopausal symptom recurrence, quality of life and the success rate of HT discontinuation between these two treatment groups |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Healthy postmenopausal women under 60 years of age who are willing to be randomized to either continue or discontinue HT. We require that the participants have used HRT at least for 3 years before entering the study and have not attempted to discontinue HT within the last 6 months, or before that, for more than 2 months. |
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E.4 | Principal exclusion criteria |
Women with any clinically significant disease or regular medication, history of cardiovascular events, smoking and body mass index over 30 kg/m2. Women with hormonal IUD or who have endometrial thickness over 6 mm when entering the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Flow-mediated dilation (FMD) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
baseline (5 +/- 1 week), 13 (+/- 1 week) |
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E.5.2 | Secondary end point(s) |
Peripheral artery tonometry (PAT); heart rate variability (HRV); carotid artery compliance; biochemical measurements including follicle stimulating hormone (FSH), luteinizing hormone (LH), estrone, estradiol, SHBG, HDL, LDL, VLDL, triglycerides, lipoprotein A, fasting glucose, Interferon-γ (IFN-γ), Monocyte chemoattractant (MCP-1), Macrophage inflammatory protein 1α (MIP-1α), Tumor necrose factor α (TNF-α), Advanced glycation end product (AGE, sRAGE), highly sensitive CRP (hsCRP), nitrite, nitrate, Asymmetric dimethyl arginine (ADMA), Endothelin-1 (ET-1), fibrinogen, plasminogen activator inhibitor-1, D-dimer, E-selectin, Intracellular cell-adhesion molecule-1 (ICAM-1), Vascular cell-adhesion molecule-1 (VCAM-1), Matrix metalloproteinases (MMPs) and Oxidized LDL (oxLDL); menopausal symptoms and quality of life (Women’s Health Questionnaire, European Quality of Life Instrument) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
baseline, 13 (+/-1) week, 19 (+/-1) week |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The last visit of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |