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

NCT05647473 | Unknown Phase 2

• 1 other identifier: AM-AD
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• The primary efficacy outcome measure will be the absolute change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Chinese version score between baseline and week 48.

  The Alzheimer's Disease Assessment Scale-Cognitive Subscale, Chinese version scale scores range from 0 to 75, with higher scores indicating better.

  Participants will be followed up for 48 weeks after baseline.

Secondary Outcomes (24)

• The absolute scores change in the Rey-Osterrieth Complex Figure Test [ROCF] recall score between baseline and week 48.

  Participants will be followed up for 48 weeks after baseline.

• The absolute scores change in the ROCF-copy score between baseline and week 48.

  Participants will be followed up for 48 weeks after baseline.

• The absolute scores change in the Clock-Drawing Test score between baseline and week 48.

  Participants will be followed up for 48 weeks after baseline.

• The absolute scores change in the Trail Making Test-A score between baseline and week 48.

  Participants will be followed up for 48 weeks after baseline.

• The absolute scores change in the Digit Span Forward score between baseline and week 48.

  Participants will be followed up for 48 weeks after baseline.

Other Outcomes (5)

• Whether the participants' vital signs were normal.

  Participants will be followed up for 48 weeks after baseline.

• Whether the participants' Electrocardiograms were normal.

  Participants will be followed up for 48 weeks after baseline.

• Whether the participants' Liver function were normal.

  Participants will be followed up for 48 weeks after baseline.

Study Arms (3)

add-on low dose Astragalus

EXPERIMENTAL

Behavioral: Routine treatment; Drug: add-on low dose Astragalus

Routine treatment

EXPERIMENTAL

Behavioral: Routine treatment

add-on high dose Astragalus

EXPERIMENTAL

Behavioral: Routine treatment; Drug: add-on high dose Astragalus

Interventions

Routine treatment 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.

Routine treatment; add-on high dose Astragalus; add-on low dose Astragalus

add-on low dose Astragalus DRUG

Participants received an additional 10g of astragalus per day.

add-on low dose Astragalus

add-on high dose Astragalus DRUG

Participants received an additional 20g of astragalus per day.

add-on high dose Astragalus

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥50 years and ≤85 years
• 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.
• Memory loss for at least 6 months, with a progressive worsening trend
• 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
• Brain magnetic resonance imaging shows the degree of hippocampal atrophy is greater than or equal to grade 1
• The modified Hachinski Ischemia Scale (m-HIS) score was \< 4 points
• 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).
• There are no obvious positive signs in nervous system examination;
• The subjects have the ability of reading, writing and communication, have a stable caregiver, accompany to attend the visit.
• 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.

You may not qualify if:

• 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
• Patients who have taken other Chinese medicine preparations in the past three months
• Allergy or contraindication of astragalus
• There are other neurological diseases that can cause brain dysfunction or cognitive impairment; Mental and neurological retardation is present; Presence of malignant tumor
• The modified Hachinski Ischemia Scale (m-HIS) score was ≥ 4 points.
• 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
• Pregnant or lactating patients;
• Patients who have participated in other clinical studies within the past 3 months

Sponsors & Collaborators

• Fujian Medical University Union Hospital: lead

Study Sites (1)

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350000, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 39176240 DERIVED

MeSH Terms

Conditions

Hypotension, Orthostatic; Alzheimer Disease

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Xiaodong Pan

CONTACT

86218341; pxd77316@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2022
• First Posted: December 12, 2022
• Study Start: February 20, 2024
• Primary Completion: May 30, 2025
• Study Completion: May 30, 2025
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)