Hormone Replacement Trial Against ALzheimers' Disease

Study Overview
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Brief Summary
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The influence of postmenopausal hormone treatment on dementia is not clear. Dysfunctions in the metabolism of amyloid in the disease of Alzheimer result in an elevated presence of degradation products in cerebrospinal fluid. The degradation products in blood will be analysed during the trial, to get better insight in menopause and the start of hormonal therapy. Postmenopausal women with and without history of breast cancer will be recruited for the trial.

Detailed Description
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The influence of postmenopausal hormone treatment on dementia is not clear. Recently an overview was published. Dysfunctions in the metabolism of amyloid in the disease of Alzheimer result in an elevated presence of degradation products in cerebrospinal fluid. There are tests developed to detect those degradation products in blood. The degradation products in blood will be analysed during the trial, to get better insight in menopause and the start of hormonal therapy. The participants will be asked to come 2 times to the hospital. At every study visit, blood will be taken and questionnaires will be completed. The first study visit will take place before the start of the hormonal treatment, the second visit will take place 6 months after the start of the hormonal treatment. There will be 30 patients included per study group. There are 10 groups in total: Postmenopausal women who start oral hormonal treatment Postmenopausal women who start transdermal hormonal treatment Postmenopausal women who start oral hormonal treatment and had a hysterectomy in their medical history Postmenopausal women who start transdermal hormonal treatment and had a hysterectomy in their medical history Postmenopausal women who start oral hormonal treatment and have an intra-uterine device Postmenopausal women who start transdermal hormonal treatment and have an intra-uterine device Postmenopausal women with breast cancer taking selective oestrogen receptor modulators Postmenopausal women with breast cancer taking aromatase inhibitors Postmenopausal women with breast cancer taking duavive Postmenopausal women with no breast cancer and do not start with hormonal therapy The questionnaires that needs to be completed are: Mini Mental State Examination (only at the first visit) Targeting Aetiology of Nocturia Guides Outcomes Short Form (TANGO-SF) (visit 1 and 2) International Consultation of Incontinence Modular Questionnaire (ICIQ) (visit 1 and 2) Perceived stress scale (Cohen) (visit 1 and 2) Pittsburgh sleep quality

Official Title
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Hormone Replacement Trial Against ALzheimers' Disease

Conditions
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Postmenopausal Symptoms, Alzheimer Disease

Intervention / Treatment
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* Procedure: blood take


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: postmenopausal women 40 - 65 years Exclusion Criteria: Longer than 10 years in menopause thyroid dysfunction hypertension medical history of psychiatric comorbidity Alcohol and/or drug abuse medical history of neurologic symptoms with cognitive symptoms

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 10 study groups: 9 groups who start with hormonal treatment and 1 control group who doesn't start with hormonal treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: oral hormonal therapy<br>Postmenopausal women who start with oral hormonal therapy (Progesteron + uterogestan) according to standard of care practice. Before the start of the treatment blood will be taken and 6 months after the start of the therapy blood will be taken for analysis. At the 2 study visits the patient will be asked to complete the questionaires (TANGO-SF, ICIQ, Cohen, Pittsburgh sleep quality). Only at the first study visit an MMSE test will be taken, to make sure the patient has no dementia. | Procedure: blood take<br>* Blood is taken to analyse degratdation products of the metabolism of amyloid<br>|
| Other: transdermal hormonal therapy<br>Postmenopausal women who start with transdermal hormonal (Oestrogel + uterogestan) therapy according to standard of care practice. Before the start of the treatment blood will be taken and 6 months after the start of the therapy blood will be taken for analysis. At the 2 study visits the patient will be asked to complete the questionaires (TANGO-SF, ICIQ, Cohen, Pittsburgh sleep quality). Only at the first study visit an MMSE test will be taken, to make sure the patient has no dementia. | Procedure: blood take<br>* Blood is taken to analyse degratdation products of the metabolism of amyloid<br>|
| Other: oral hormonal therapy + hysterectomy<br>Postmenopausal women who start with oral hormonal therapy (progesteron) according to standard of care practice and had a hysterectomy in the past. Before the start of the treatment blood will be taken and 6 months after the start of the therapy blood will be taken for analysis. At the 2 study visits the patient will be asked to complete the questionaires (TANGO-SF, ICIQ, Cohen, Pittsburgh sleep quality). Only at the first study visit an MMSE test will be taken, to make sure the patient has no dementia. | Procedure: blood take<br>* Blood is taken to analyse degratdation products of the metabolism of amyloid<br>|
| Other: transdermal hormonal therapy + hysterectomy<br>Postmenopausal women who start with transdermal hormonal therapy (Oestrogel ) according to standard of care practice and had a hysterectomy in the past. Before the start of the treatment blood will be taken and 6 months after the start of the therapy blood will be taken for analysis. At the 2 study visits the patient will be asked to complete the questionaires (TANGO-SF, ICIQ, Cohen, Pittsburgh sleep quality). Only at the first study visit an MMSE test will be taken, to make sure the patient has no dementia. | Procedure: blood take<br>* Blood is taken to analyse degratdation products of the metabolism of amyloid<br>|
| Other: oral hormonal therapy + IUD<br>Postmenopausal women who start with oral hormonal therapy (Progynova) according to standard of care practice and have already an intra-uterine device. Before the start of the treatment blood will be taken and 6 months after the start of the therapy blood will be taken for analysis. At the 2 study visits the patient will be asked to complete the questionaires (TANGO-SF, ICIQ, Cohen, Pittsburgh sleep quality). Only at the first study visit an MMSE test will be taken, to make sure the patient has no dementia. | Procedure: blood take<br>* Blood is taken to analyse degratdation products of the metabolism of amyloid<br>|
| Other: transdermal hormonal therapy + IUD<br>Postmenopausal women who start with transdermal hormonal therapy (Oestrogel ) according to standard of care practice and have an intra-uterine device. Before the start of the treatment blood will be taken and 6 months after the start of the therapy blood will be taken for analysis. At the 2 study visits the patient will be asked to complete the questionaires (TANGO-SF, ICIQ, Cohen, Pittsburgh sleep quality). Only at the first study visit an MMSE test will be taken, to make sure the patient has no dementia. | Procedure: blood take<br>* Blood is taken to analyse degratdation products of the metabolism of amyloid<br>|
| Other: selective oestrogenreceptor modulators<br>Postmenopausal women who start with hormonal therapy according to standard of care practice and take selective oestrogenreceptor modulators (Nolvadex) because of their cancer in their medical history. Before the start of the treatment blood will be taken and 6 months after the start of the therapy blood will be taken for analysis. At the 2 study visits the patient will be asked to complete the questionaires (TANGO-SF, ICIQ, Cohen, Pittsburgh sleep quality). Only at the first study visit an MMSE test will be taken, to make sure the patient has no dementia. | Procedure: blood take<br>* Blood is taken to analyse degratdation products of the metabolism of amyloid<br>|
| Other: aromatase inhibitors<br>Postmenopausal women who start with hormonal therapy according to standard of care practice and who taken aromatase inhibitors (Femara) because of their cancer in their medical history. Before the start of the treatment blood will be taken and 6 months after the start of the therapy blood will be taken for analysis. At the 2 study visits the patient will be asked to complete the questionaires (TANGO-SF, ICIQ, Cohen, Pittsburgh sleep quality). Only at the first study visit an MMSE test will be taken, to make sure the patient has no dementia. | Procedure: blood take<br>* Blood is taken to analyse degratdation products of the metabolism of amyloid<br>|
| Other: Duavive<br>Postmenopausal women who start with hormonal therapy according to standard of care practice and who take duavive because of their cancer in their medical history. Before the start of the treatment blood will be taken and 6 months after the start of the therapy blood will be taken for analysis. At the 2 study visits the patient will be asked to complete the questionaires (TANGO-SF, ICIQ, Cohen, Pittsburgh sleep quality). Only at the first study visit an MMSE test will be taken, to make sure the patient has no dementia. | Procedure: blood take<br>* Blood is taken to analyse degratdation products of the metabolism of amyloid<br>|
| Other: Control<br>Postmenopausal women who don't start with hormonal therapy according to standard of care practice. At the first study visit blood will be taken and 6 months after the start of the therapy blood will be taken for analysis. At the 2 study visits the patient will be asked to complete the questionaires (TANGO-SF, ICIQ, Cohen, Pittsburgh sleep quality). Only at the first study visit an MMSE test will be taken, to make sure the patient has no dementia. | Procedure: blood take<br>* Blood is taken to analyse degratdation products of the metabolism of amyloid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degradation products of the Amyloid metabolism in blood | The influence of hormone treatment (menopause) and anti-hormone treatment (breastcancer) on the amyloid metabolism and the development of Alzheimer will be evaluated. Different laboratory analysis will be performed to evaluate the degradation products of the metabolism of amyloid in blood. Different parts of the degradation products will be analysed namely: Plasma total-tau | 2 years after the first patient was included, the first batch of samples will be analysed. | 
| Degradation products of the Amyloid metabolism in blood | The influence of hormone treatment (menopause) and anti-hormone treatment (breastcancer) on the amyloid metabolism and the development of Alzheimer will be evaluated. Different laboratory analysis will be performed to evaluate the degradation products of the metabolism of amyloid in blood. Different parts of the degradation products will be analysed namely: Nurofilament light chain | 2 years after the first patient was included, the first batch of samples will be analysed. | 
| Degradation products of the Amyloid metabolism in blood | The influence of hormone treatment (menopause) and anti-hormone treatment (breastcancer) on the amyloid metabolism and the development of Alzheimer will be evaluated. Different laboratory analysis will be performed to evaluate the degradation products of the metabolism of amyloid in blood. Different parts of the degradation products will be analysed namely: Abeta1-40 | 2 years after the first patient was included, the first batch of samples will be analysed. | 
| Degradation products of the Amyloid metabolism in blood | The influence of hormone treatment (menopause) and anti-hormone treatment (breastcancer) on the amyloid metabolism and the development of Alzheimer will be evaluated. Different laboratory analysis will be performed to evaluate the degradation products of the metabolism of amyloid in blood. Different parts of the degradation products will be analysed namely: Abeta1-42 | 2 years after the first patient was included, the first batch of samples will be analysed. | 
| Degradation products of the Amyloid metabolism in blood | The influence of hormone treatment (menopause) and anti-hormone treatment (breastcancer) on the amyloid metabolism and the development of Alzheimer will be evaluated. Different laboratory analysis will be performed to evaluate the degradation products of the metabolism of amyloid in blood. Different parts of the degradation products will be analysed namely: YKL-40 | 2 years after the first patient was included, the first batch of samples will be analysed. | 
| Degradation products of the Amyloid metabolism in blood | The influence of hormone treatment (menopause) and anti-hormone treatment (breastcancer) on the amyloid metabolism and the development of Alzheimer will be evaluated. Different laboratory analysis will be performed to evaluate the degradation products of the metabolism of amyloid in blood. Different parts of the degradation products will be analysed namely: Neurogranin | 2 years after the first patient was included, the first batch of samples will be analysed. | 
| APOE-genotyping in blood | The influence of hormone treatment (menopause) and anti-hormone treatment (breastcancer) on the amyloid metabolism and the development of Alzheimer will be evaluated. APOE-genotyping will be performed | 2 years after the first patient was included, the first batch of samples will be analysed. | 
| identify BACE1 in blood | The influence of hormone treatment (menopause) and anti-hormone treatment (breastcancer) on the amyloid metabolism and the development of Alzheimer will be evaluated. BACE1 will also be identified in the blood. | 2 years after the first patient was included, the first batch of samples will be analysed. |