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

Phase 2

Recruiting

• Conditions: Orthostatic Hypotension; Alzheimer Disease
• Interventions: Behavioral: Routine treatment; Drug: add-on low dose Astragalus; Drug: add-on high dose Astragalus

• Registration Number: NCT05647473
• Lead Sponsor: Fujian Medical University Union Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-12-04
• Study First Submitted QC: 2022-12-04
• Study First Posted: 2022-12-12
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-02
• Last Update Posted: 2024-01-05
• Study Start: 2024-02-20
• Primary Completion: 2025-05-30
• Study Completion: 2025-05-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

The inclusion criteria will be as follows:

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

The exclusion criteria will be as follows:

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
add-on low dose Astragalus	add-on low dose Astragalus	-
add-on low dose Astragalus	Routine treatment	-
add-on high dose Astragalus	add-on high dose Astragalus	-
Routine treatment	Routine treatment	-
add-on high dose Astragalus	Routine treatment	-

Primary Outcome Measures

Name	Time	Method
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.	Participants will be followed up for 48 weeks after baseline.	The Alzheimer's Disease Assessment Scale-Cognitive Subscale, Chinese version scale scores range from 0 to 75, with higher scores indicating better.

Secondary Outcome Measures

Name	Time	Method
The absolute change in the blood pressure between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	To observe the changes of orthostatic blood pressure in patients
The absolute change in the level of plasma β-amyloid40 (ng/ml) between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	Amyloid is one of the main biomarkers of dementia
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 Trail Making Test-A scores range from 0 to 25, with higher scores indicating better.
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 Clock-Drawing Test scale scores range from 0 to 5, with higher scores indicating better.
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.	TheDigit Span Forward score scores range from 0 to 10, with higher scores indicating better.
The absolute scores change in the Hamilton Depression Scale score between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	The Hamilton Anxiety Scale score scores range from 0 to 96, with higher scores indicating worse.
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 ROCF scale scores range from 0 to 36, with higher scores indicating better.
The absolute scores change in the Digit Span Backward score between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	TheDigit Span Forward score scores range from 0 to 9, with higher scores indicating better.
The absolute scores change in the Hamilton Anxiety Scale score between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	The Hamilton Anxiety Scale score scores range from 0 to 56, with higher scores indicating worse.
The absolute change in the level of plasma neurofilament light chain (ng/ml) between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	Neurofilament light chain is one of the main biomarkers of dementia
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 ROCF copy scale scores range from 0 to 36, with higher scores indicating better.
The absolute scores change in the Trail Making Test-B score between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	The Trail Making Test-B scores range from 0 to 25, with higher scores indicating better.
The absolute scores change in the Verbal Fluency Test score between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	The Verbal Fluency Test score scores range from 0 to 14, with higher scores indicating better.
The absolute change in the neurite density index between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	Neurite density index is the main indicator of neurite-oriented diffusion and density imaging (NODDI) .
The absolute change in the isotropic volume fraction between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	Isotropic volume fraction is the main indicator of neurite-oriented diffusion and density imaging (NODDI) .
The absolute change in the level of plasma hyper-phosphorylated tau-181 (ng/ml) between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	Neurofilament light chain is one of the main biomarkers of dementia
The absolute change in the P300 between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	P300 is the main indicator of EEG, and its normal value range is between 320 and 420.
The absolute change in the VP300 between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	VP300 is the main indicator of EEG, and its normal value range is between 320 and 420.
The absolute change in theheart rate variability between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	The KARDi2/4-B autonomic nervous function mapping ECG system (Nanjing Left and Right Brain Biomedical Company, NeuroMed, China) will record and analyze millivolt-level signals of ECG oscillations, complete the frequency domain and time domain index detection of heart rate variability in 3 min, and generate an autonomic nervous function status step map.
The absolute change in the level of plasma β-amyloid42 (ng/ml) between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	Amyloid is one of the main biomarkers of dementia
The absolute change in the MMN between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	MMN is the main indicator of EEG, and its normal value range is between 100 and 210.
The absolute change in the orientation dispersion index between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	Orientation dispersion index is the main indicator of neurite-oriented diffusion and density imaging (NODDI) .
The absolute change in the Montreal Cognitive Assessment(MOCA) score between baseline and week 48.	Participants will be followed up for48 weeks after baseline.	The Alzheimer's Disease Assessment Scale-Cognitive Subscale, Chinese version scale scores range from 0 to 30, with higher scores indicating better.
The absolute change in the level of plasma glial fibrillary acidic protein (ng/ml) between baseline and week 48.	Participants will be followed up for 48 weeks after baseline.	Glial fibrillary acidic protein is one of the main biomarkers of dementia

Trial Locations

Locations (1)

Fujian Medical University Union Hospital; 🇨🇳 Fuzhou, Fujian, China