Effect of Menopause Hormone Therapy In Postmenopausal Women With CSVD And MCI

NCT05982470 | Unknown Phase 2 DMC

• 1 other identifier: KY2023-117
• Study Type: interventional
• Target: 328
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this clinical trial is to explore the efficacy of menopausal hormone therapy in early menopausal women with CSVD and MCI. The main questions it aims to answer are:

• The efficacy of menopausal hormone mainly estrogen therapy for early menopausal women with CSVD and MCI
• The role of MHT in delaying the progression of cognitive function, CSVD imaging features, and other clinical symptoms and the potential pathophysiological mechanisms. Participants will be divided randomly into two groups taking MHT drugs and placebo respectively and followed up for 12 months to collect relevant clinical data.

Conditions

Cerebral Small Vessel Diseases; Postmenopausal Symptoms; Mild Cognitive Impairment; White Matter Hyperintensity

Keywords

cerebral small vessel diseases; Menopausal Hormone Therapy; Postmenopausal Symptoms; Mild Cognitive Impairment; White Matter Hyperintensity

Outcome Measures

Primary Outcomes (1)

• the changes in the Montreal Cognitive Assessment (MoCA; range, 0-30; with lower scores indicating more severe cognitive impairment) scores 1 year after randomization compared to baseline

  the changes of the Montreal Cognitive Assessment (MoCA; range, 0-30; with lower scores indicating more severe cognitive impairment) scores

  1 year after randomization

Secondary Outcomes (8)

• the changes in each cognitive domain estimated bythe Montreal Cognitive Assessment (MoCA; range, 0-30; with lower scores indicating more severe cognitive impairment) sub-items 1 year after randomization compared to baseline

  1 year after randomization

• the changes of modified Kupperman scores (0-63; with higher scores indicating more severe symptoms) 1 year after randomization compared to baseline

  1 year after randomization

• the changes of Pittsburgh sleep quality index(PSQI; with higher scores indicating more severe sleep quality) 1 year after randomization compared to baseline

  1 year after randomization

• the changes of Hamilton Depression Scale(HAMD; ranges, 0-54; with higher scores indicating more severe depression) 1 year after randomization compared to baseline

  1 year after randomization

• the changes of Hamilton Anxiety Scale(HAMA; ranges, 0-56; with higher scores indicating more severe anxiety) 1 year after randomization compared to baseline

  1 year after randomization

Other Outcomes (1)

• the incidence of combined outcome (including recent small subcortical infarct and combined vascular events) 1 year after randomization

  1 year after randomization

Study Arms (2)

treatment group

EXPERIMENTAL

Estradiol gel 2.5 g (containing 17β estradiol 1.5mg) once daily (percutaneous application)\* in combination with progesterone soft capsules 100mg once daily (oral) for 12 months Note : \* Usage and dosage of estradiol gel: A dose of ruler is applied to the skin of the arm, shoulder, head and neck, abdomen, thigh or face every morning or evening. It is dry about two minutes after application. It is non-irritating, colorless, or milky white and tasteless, and is best used after bathing.

Drug: Estradiol Gel; Drug: Progesterone Soft Capsule

control group

PLACEBO COMPARATOR

Estradiol placebo gel 2.5g (containing 17β estradiol 0mg) once daily (percutaneous application) \*in combination with progesterone placebo soft capsules(containing progesterone 0mg) 100mg once daily (oral) for 12 months Note : \* Usage and dosage of estradiol placebo gel : A dose of ruler is applied to the skin of the arm, shoulder, head and neck, abdomen, thigh or face every morning or evening. It is dry about two minutes after application. It is non-irritating, colorless, or milky white and tasteless, and is best used after bathing.

Drug: Estradiol Placebo Gel; Drug: Progesterone Placebo Soft Capsule

Interventions

Estradiol Gel DRUG

Estradiol gel 2.5 g (containing 17β estradiol 1.5mg) once daily (percutaneous application) for 12 months

treatment group

Estradiol Placebo Gel DRUG

Estradiol placebo gel 2.5 g (containing 17β estradiol 1.5mg) once daily (percutaneous application) for 12 months

control group

Progesterone Soft Capsule DRUG

Progesterone soft capsules 100mg once daily (oral) for 12 months

treatment group

Progesterone Placebo Soft Capsule DRUG

Progesterone placebo soft capsules 100mg once daily (oral) for 12 months

control group

Eligibility Criteria

• Age: 40 Years - 60 Years
• Gender Eligibility Details: Early menopause of female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• ≤ age \< 60 years
• Female;
• year ≤ Natural menopause≤ 6 years;
• FSH ≥ 35 miu/ml and E2 ≤ 25 pg/ml;
• Head MRI shows CSVD-related image changes, meet one of the following:
• Parventricular or deep brain white matter hyperintense, Fazekas ≥ 2；
• Parventricular or deep brain white matter hyperintense, Fazekas = 1, with more than 2 vascular risk factors (hypertension, hyperlipidemia, type 2 diabetes, obesity, current smoking);
• Parventricular or deep brain white matter hyperintense, Fazekas = 1, with more than 1 vascular-derived lacunae;
• Recent small subcortical infarction within the last 3 months
• Mild cognitive dysfunction (18 ≤ MoCA \<26);
• Independent in daily life (mRS ≤ 1）
• Sign informed consent.
• Note:
• Natural menopause: The self-reported last menstrual date of the subject
• CSVD related image changes: evaluated according to the STRIVE2 standard issued in 2023;

You may not qualify if:

• Inheritable CSVD, such as CADASIL, CARASIL, etc.
• Confirmed neurodegenerative diseases, such as AD and PD;
• Clear non-vascular white matter lesions, such as multiple sclerosis, adult brain white matter dysplasia, metabolic encephalopathy, etc.
• History of intracranial hemorrhagic disease within the recent 6 months, including cerebral parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural / extradural hematoma, etc., as well as untreated aneurysms (diameter\> 3mm) and cerebrovascular malformations.
• Cardiovascular and cerebrovascular events within the past 6 months, such as myocardial infarction, unstable angina pectoris, cerebral infarction, etc.
• Previously received or initiated menopausal hormone therapy.
• Previous Hysterectomy
• Vaginal bleeding of unknown origin
• Intra- and extra- cranial Atherosclerosis large artery stenosis (50-99%) or occlusion.
• Active venous or arterial thromboembolic diseases, such as Deep vein thrombosis, Pulmonary embolism, myocardial infarction, angina pectoris or congestive heart failure, in the last 6 months.
• Used drugs and Phytoestrogen supplements that affect estrogen levels in the past 3 months, such as soybean concentrate or extract, Kuntai capsule, Dingkundan, Lifumin, etc.
• Endometrial hyperplasia, vaginal ultrasound indicates endometrial ≥ 5mm (note: those confirmed as benign lesions by pathology can be included).
• Severe liver and kidney dysfunction: severe liver dysfunction refers to Alanine transaminase\>3 times the upper limit of normal value or cereal grass Transaminase\>3 times the upper limit of normal value; Severe renal insufficiency refers to blood creatinine\>3.0 mg/dl (265.2 μmol/L) or glomerular filtration rate\<30 ml/min/1.73m\^2;
• Hypertension is still difficult to control after standardized treatment (blood pressure\>160/100mmHg); Type 2 diabetes is still difficult to control after standard treatment (Glycated hemoglobin ≥ 8%).
• Known or suspected to have sex hormone dependent malignant tumors, such as breast cancer, endometrial cancer, cervical adenocarcinoma, ovarian cancer, and meningioma.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, China

Location

MeSH Terms

Conditions

Cerebral Small Vessel Diseases; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• yilong wang, MD,PhD

  Beiiing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

yilong wang, MD,PhD

CONTACT

0086-010-67092222; yilong528@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President of Beijing Tiantan Hospital

Study Record Dates

• First Submitted: July 18, 2023
• First Posted: August 8, 2023
• Study Start: August 18, 2023
• Primary Completion: June 1, 2025
• Study Completion: October 1, 2025
• Last Updated: August 8, 2023

Record last verified: 2023-08

Locations

CN (1)