Clinical trial NCT05647473: Efficacy, Safety and Response Predictors of Adjuvant Astragalus for Cognition in Orthostatic Hypotension
Official title: Efficacy, Safety and Response Predictors of Adjuvant Astragalus for Cognition in Alzheimer Disease With Orthostatic Hypotension: an add-on, Assessor-blind, Pragmatic Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Orthostatic Hypotension
Alzheimer Disease
Lead sponsor: Fujian Medical University Union Hospital
Sponsor class: OTHER
First posted: 2022-12-12
Enrollment: 66
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Participants will be followed up for 48 weeks after baseline.
Secondary outcomes:
measure: The absolute scores change in the Rey-Osterrieth Complex Figure Test [ROCF] recall score between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute scores change in the ROCF-copy score between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute scores change in the Clock-Drawing Test score between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute scores change in the Trail Making Test-A score between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute scores change in the Digit Span Forward score between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute scores change in the Trail Making Test-B score between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute scores change in the Digit Span Backward score between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute scores change in the Verbal Fluency Test score between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute scores change in the Hamilton Anxiety Scale score between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute scores change in the Hamilton Depression Scale score between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in the blood pressure between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in the level of plasma β-amyloid40 (ng/ml) between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in the level of plasma β-amyloid42 (ng/ml) between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in the level of plasma glial fibrillary acidic protein (ng/ml) between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in the level of plasma neurofilament light chain (ng/ml) between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in the level of plasma hyper-phosphorylated tau-181 (ng/ml) between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in the P300 between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in the VP300 between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in the MMN between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in the neurite density index between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in the orientation dispersion index between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in the isotropic volume fraction between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in theheart rate variability between baseline and week 48.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: The absolute change in the Montreal Cognitive Assessment(MOCA) score between baseline and week 48.
timeFrame: Participants will be followed up for48 weeks after baseline.
Other outcomes:
measure: Whether the participants' vital signs were normal.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: Whether the participants' Electrocardiograms were normal.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: Whether the participants' Liver function were normal.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: Whether the participants' kidney function were normal.
timeFrame: Participants will be followed up for 48 weeks after baseline.
measure: Severity of adverse events
timeFrame: Participants will be followed up for 48 weeks after baseline.
Locations:
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
Study officials:
References: