Hormone Replacement Trial Against ALzheimers' Disease (HARALD)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease; Postmenopausal Symptoms
• Intervention / Treatment: Procedure: blood take

Detailed Description

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:

1. Postmenopausal women who start oral hormonal treatment
2. Postmenopausal women who start transdermal hormonal treatment
3. Postmenopausal women who start oral hormonal treatment and had a hysterectomy in their medical history
4. Postmenopausal women who start transdermal hormonal treatment and had a hysterectomy in their medical history
5. Postmenopausal women who start oral hormonal treatment and have an intra-uterine device
6. Postmenopausal women who start transdermal hormonal treatment and have an intra-uterine device
7. Postmenopausal women with breast cancer taking selective oestrogen receptor modulators
8. Postmenopausal women with breast cancer taking aromatase inhibitors
9. Postmenopausal women with breast cancer taking duavive
10. Postmenopausal women with no breast cancer and do not start with hormonal therapy

The questionnaires that needs to be completed are:

1. Mini Mental State Examination (only at the first visit)
2. Targeting Aetiology of Nocturia Guides Outcomes Short Form (TANGO-SF) (visit 1 and 2)
3. International Consultation of Incontinence Modular Questionnaire (ICIQ) (visit 1 and 2)
4. Perceived stress scale (Cohen) (visit 1 and 2)
5. Pittsburgh sleep quality

• Study Type: Interventional
• Enrollment (Actual): 421
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eline Meireson, Msc; Phone Number: 0032 9 332 78 17; Email: eline.meireson@uzgent.be

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Ghent University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: oral hormonal therapy; 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; Blood is taken to analyse degratdation products of the metabolism of amyloid
Other: transdermal hormonal therapy; 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; Blood is taken to analyse degratdation products of the metabolism of amyloid
Other: oral hormonal therapy + hysterectomy; 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; Blood is taken to analyse degratdation products of the metabolism of amyloid
Other: transdermal hormonal therapy + hysterectomy; 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; Blood is taken to analyse degratdation products of the metabolism of amyloid
Other: oral hormonal therapy + IUD; 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; Blood is taken to analyse degratdation products of the metabolism of amyloid
Other: transdermal hormonal therapy + IUD; 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; Blood is taken to analyse degratdation products of the metabolism of amyloid
Other: selective oestrogenreceptor modulators; 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; Blood is taken to analyse degratdation products of the metabolism of amyloid
Other: aromatase inhibitors; 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; Blood is taken to analyse degratdation products of the metabolism of amyloid
Other: Duavive; 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; Blood is taken to analyse degratdation products of the metabolism of amyloid
Other: Control; 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; Blood is taken to analyse degratdation products of the metabolism of amyloid

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Herman Depypere, MD, University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2018
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 8, 2020
• First Submitted That Met QC Criteria: March 17, 2020
• First Posted (Actual): March 18, 2020

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: EC/2018/0315

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No