Efficacy, Safety and Response Predictors of Adjuvant Astragalus for Cognition in Orthostatic Hypotension

NCT ID: NCT05647473

Last Updated: 2024-01-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-20
• Study Completion Date: 2025-05-30

Brief Summary

Background: This pragmatic clinical trial aims to determine the efficacy and safety of add-on Astragalus for cognition and non- cognition in patients with of mild to moderate Alzheimer's disease complicated with orthostatic hypotension in orthostatic hypotension, elucidate the underlying mechanisms, identify related response predictors, and explore effective drug components.

Methods: This is an add-on, assessor-blinded, parallel, pragmatic, randomized controlled trial. At least 66 adults with mild to moderate Alzheimer's disease (AD) and OH aged >30 years will be recruited. Participants will be randomized in a 1:1:1 ratio to receive 24 weeks of routine care or add-on low dose Astragalus or high dose Astragalus group. The primary efficacy outcome will be measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Chinese version. Secondary efficacy outcome assessment will include neuropsychological tests, blood pressure, plasma biomarkers, multimodal electroencephalograms, and neuroimaging. Safety outcome measures will include physical examinations, vital signs, electrocardiography, laboratory tests (such as hematologic and blood chemical tests), and adverse event records.

Conditions

Orthostatic Hypotension; Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

add-on low dose Astragalus

Group Type: EXPERIMENTAL

Routine treatment

Intervention Type: BEHAVIORAL

Participants will be educated on ways to avoid induced hypotensive states, such as avoiding prolonged standing, standing after exercise, being nervous, eating several carbohydrate-rich foods, drinking alcohol, and being in a warm environment (such as a sauna). Participants will be encouraged in a comfortable home environment, such as a sit-down bath. If there are no contraindications, they are advised to increase their salt intake to approximately 10 grams per day and adjust their fluid intake to 2-3 liters per day. They will also be encouraged to perform lower-body strength training and moderate, non-strenuous activities. Seriously ill patients will be proposed to raise the head of their bed during sleep, wear tight clothing, eat small meals, and reduce alcohol intake.Concomitant treatment with cholinesterase inhibitors, memantine, or both was allowed.

add-on low dose Astragalus

Intervention Type: DRUG

Participants received an additional 10g of astragalus per day.

Routine treatment

Group Type: EXPERIMENTAL

Routine treatment

Intervention Type: BEHAVIORAL

Participants will be educated on ways to avoid induced hypotensive states, such as avoiding prolonged standing, standing after exercise, being nervous, eating several carbohydrate-rich foods, drinking alcohol, and being in a warm environment (such as a sauna). Participants will be encouraged in a comfortable home environment, such as a sit-down bath. If there are no contraindications, they are advised to increase their salt intake to approximately 10 grams per day and adjust their fluid intake to 2-3 liters per day. They will also be encouraged to perform lower-body strength training and moderate, non-strenuous activities. Seriously ill patients will be proposed to raise the head of their bed during sleep, wear tight clothing, eat small meals, and reduce alcohol intake.Concomitant treatment with cholinesterase inhibitors, memantine, or both was allowed.

add-on high dose Astragalus

Group Type: EXPERIMENTAL

Routine treatment

Intervention Type: BEHAVIORAL

Participants will be educated on ways to avoid induced hypotensive states, such as avoiding prolonged standing, standing after exercise, being nervous, eating several carbohydrate-rich foods, drinking alcohol, and being in a warm environment (such as a sauna). Participants will be encouraged in a comfortable home environment, such as a sit-down bath. If there are no contraindications, they are advised to increase their salt intake to approximately 10 grams per day and adjust their fluid intake to 2-3 liters per day. They will also be encouraged to perform lower-body strength training and moderate, non-strenuous activities. Seriously ill patients will be proposed to raise the head of their bed during sleep, wear tight clothing, eat small meals, and reduce alcohol intake.Concomitant treatment with cholinesterase inhibitors, memantine, or both was allowed.

add-on high dose Astragalus

Intervention Type: DRUG

Participants received an additional 20g of astragalus per day.

Interventions

Routine treatment

Participants will be educated on ways to avoid induced hypotensive states, such as avoiding prolonged standing, standing after exercise, being nervous, eating several carbohydrate-rich foods, drinking alcohol, and being in a warm environment (such as a sauna). Participants will be encouraged in a comfortable home environment, such as a sit-down bath. If there are no contraindications, they are advised to increase their salt intake to approximately 10 grams per day and adjust their fluid intake to 2-3 liters per day. They will also be encouraged to perform lower-body strength training and moderate, non-strenuous activities. Seriously ill patients will be proposed to raise the head of their bed during sleep, wear tight clothing, eat small meals, and reduce alcohol intake.Concomitant treatment with cholinesterase inhibitors, memantine, or both was allowed.

Intervention Type: BEHAVIORAL

add-on low dose Astragalus

Participants received an additional 10g of astragalus per day.

Intervention Type: DRUG

add-on high dose Astragalus

Participants received an additional 20g of astragalus per day.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male or female aged ≥50 years and ≤85 years

2. A decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within 3 minutes after standing.

3. Memory loss for at least 6 months, with a progressive worsening trend

4. Patients with mild or moderate disease degree, that is, the total score of MMSE: 14 points < total score of MMSE <24 points, 0.5≤CDR≤2 points, and the total score of HAMD (24-item version) ≤20 points

5. Brain magnetic resonance imaging shows the degree of hippocampal atrophy is greater than or equal to grade 1

6. The modified Hachinski Ischemia Scale (m-HIS) score was < 4 points

7. The criteria described by the diagnostic and statistical manual of mental disorder-V for the diagnosis of dementia comply with the National Institute on Aging - Alzheimer's Association "Very likely AD" (National Institute of Aging-Alzheimer's Association, 2011).

8. There are no obvious positive signs in nervous system examination;

9. The subjects have the ability of reading, writing and communication, have a stable caregiver, accompany to attend the visit.

10. The basic treatment of AD before enrollment remained unchanged, and if long-term users needed to use it steadily for more than 4 weeks before randomization,the dose was kept as stable as possible during the study. Such drugs include: cholinesterase inhibitors and diamantine.

Exclusion Criteria

1. MRI showed significant focal lesions, including one of the following: a. There were more than 2 infarcts with a diameter greater than 2cm; b. Infarcts in key areas such as the thalamus, hippocampus, entorhinal cortex, parorhinal cortex, angular gyrus, cortex, and other subcortical gray matter nuclei; c. White matter lesion Fazekas Scale ≥3

2. Patients who have taken other Chinese medicine preparations in the past three months

3. Allergy or contraindication of astragalus

4. There are other neurological diseases that can cause brain dysfunction or cognitive impairment; Mental and neurological retardation is present; Presence of malignant tumor

5. The modified Hachinski Ischemia Scale (m-HIS) score was ≥ 4 points.

6. Patients who refuse or have MRI or EEG contraindications (pacemakers, coronary and peripheral arterial stents, Metal implants, claustrophobia, or severe visual or hearing impairment), refusing to draw blood

7. Pregnant or lactating patients;

8. Patients who have participated in other clinical studies within the past 3 months

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fujian Medical University Union Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xiaodong Pan

Role: CONTACT

pxd77316@163.com

86218341

Facility Contacts

Xiaodong Pan

Role: primary

xieheyb@163.com

86218341

References

Cheng Y, Lin L, Huang P, Zhang J, Pan X. Efficacy, safety, and response predictors of Astragalus in patients with mild to moderate Alzheimer's disease: A study protocol of an assessor-blind, statistician-blind open-label randomized controlled trial. Contemp Clin Trials Commun. 2024 Jul 28;41:101339. doi: 10.1016/j.conctc.2024.101339. eCollection 2024 Oct.

Reference Type: DERIVED

PMID: 39176240 (View on PubMed)

Other Identifiers

AM-AD

Identifier Type: -

Identifier Source: org_study_id