Feru-guard for Behavioral Symptoms in Dementia

Study Overview
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Brief Summary
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This is designed as a randomized, double-blind, placebo-controlled clinical trial with a 12 week intervention period. Seventy participants with a diagnosis of AD, vascular, and mixed dementia with at least 3 behavioral symptoms present from the Neuropsychiatric Inventory Questionnaires (NPI-Q) will be randomized to the Feru-guard (ferulic acid and Angelica archangelica) or placebo group. Participants will be screened first by a telephone interview or briefly in-clinic and then will be scheduled for an in-clinic screen to establish study eligibility prior to the baseline assessment visit. Clinical and biological outcome measures will occur at baseline and 12 weeks.

Detailed Description
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The participants will be assessed for eligibility using the NPI-Q and must have at least 3 symptoms present, and a score of 25 or lower on the Mini Mental State Exam (MMSE). Participants will also be screened for a previous diagnosis of either Vascular Dementia, Alzheimer's disease, or Mixed Dementia using DSM-5 criteria. The primary outcome measure will be a change in the total score of Neuropsychiatric Inventory Questionnaire (NPI-Q) over 12-weeks. The investigators expect the group receiving Feru-guard will have a greater improvement in total NPI score compared to the placebo group at 12-weeks. The investigators will also collect data on the effect of Feru-guard supplementation on care-giver burden using the NPI-Q subscale of caregiver distress, Zarit Burden Interview (ZBI) screening version, and quality of life (SF-12) over 12 weeks. The investigators will also collect data on changes in global cognition of participants over 12 weeks using the Montreal Cognitive Assessment (MoCA). The investigators will compare secondary outcomes between Feru-guard and control group.

Official Title
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Feru-guard (Ferulic Acid and Angelica Archangelica Extract) for Behavioral Symptoms in Dementia

Conditions
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Behavioral and Psychiatric Symptoms of Dementia

Intervention / Treatment
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* Drug: Feru-guard 100M
* Other: Feru-guard 100M Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 55 years old or older. Diagnosis of AD, vascular, and mixed dementia Neuropsychiatric Inventory Questionnaire (NPI-Q) at least 3 items out of 12 items are rated as present. Use of cholinesterase inhibitors, antidepressants and or antipsychotics medications is allowed, if on stable dosage for at least 2 months. Use of memantine and/or serotonin reuptake inhibitors is also allowed, if on stable dose for at least 2 months. Have a committed caregiver who is able and willing to assist them with medications, provide study participant information, and attend all study visits. Sufficient English language skills to complete all testing. MMSE score of 25 or lower. Exclusion Criteria: Participants who started using antipsychotics or anticholinergics within the previous 2 months. Participants on blood thinners such as warfarin (Coumadin, jantoven), rivaroxaban (xarelto), fondaparinux (arixtra), dibigatran (pradaxa), apixaban (eliquis) dalteparin (fragmin), enoxaparin (lovenox). Aspirin use is allowed. Participants without an identified caregiver. Participants with delirium caused by medicinal poisoning or drug intoxication. Participants who have had the following diseases before the onset of cognitive impairment: Alcoholism Manic depression or bipolar disorder Schizophrenia Participants with malignancy or an acute inflammatory disease. Participants with critical circulatory, respiratory, kidney, or liver disease or diabetes. BMI of >30. Participants who have taken Feru-guard, ferulic acid, or Angelica archangelica supplementation within the last year. Enrollment in another clinical trial or treatment study within the previous 6 months.

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled clinical trial with a 12 week intervention period.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Feru-guard<br>Over a 12 week period participants will take two 280 mg hard gel capsules of Feru-guard 100M per day (1 capsule am, 1 capsule pm). One capsule will be taken in the morning with a meal and one capsule will be taken in the afternoon with a meal. Each capsule contains 180.32 mg ferulic acid and 20.02 mg of Angelica archangelica. Total daily dose will be 560mg of Feru-guard 100M, with 360.64 mg of ferulic acid and 40.04 mg of Angelica archangelica. | Drug: Feru-guard 100M<br>* Feru-guard is a dietary supplement commercially available in Japan in the form of a 1.5 g instant powder packet that is sold in health clinics and directly by Glovia Co. Ltd to patients on doctor's recommendation. The current study will use Feru-guard in the form of a 280 mg hard gel capsule that contains the same amount of the active ingredients (ferulic acid and Angelica archangelica) as the 1.5 g packets. In order to conduct a double-blind, placebo-controlled trial, Feru-guard is contained in opaque, hard gel capsules which allows for better matching of characteristics and improved blinding than studies using powder. Feru-guard will be supplied by Glovia, Co. Ltd., in Tokyo, Japan.<br>|
| Placebo Comparator: Placebo<br>Over a 12 week period participants will take two 280 mg hard gel capsules of a placebo per day (1 capsule am, 1 capsule pm). One capsule will be taken in the morning with a meal and one capsule will be taken in the afternoon with a meal.Total daily dosage will be 560mg of a maltodextrin, calcium stearate, and vanilla food flavor mixture. | Other: Feru-guard 100M Placebo<br>* In order to conduct a double-blind, controlled trial, the placebo will be contained in opaque, hard gel capsules which allows for better matching of characteristics and improved blinding. The placebo study drug will be matched to the Feru-guard 100M in terms of appearance, smell, and taste.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline Neuropsychiatric Inventory Questionnaire at 12 weeks | The NPI-Q is a structured interview with a caregiver or qualified study partner (defined as having direct contact > 2 days/week) that evaluates both presence and severity of 12 neuropsychiatric features which include: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability, lability, apathy, aberrant motor behavior, night-time behavior, and appetite/ eating changes. If the response to the domain question is No, the informant goes to the next question. If Yes, the informant then rates both the Severity of the symptoms present within the last month on a 3-point scale ranging from 1 to 3 (mild to severe). Change in overall NPI-Q score between baseline and at 12 weeks will be the primary outcome measure. | Administered 2 times 1 baseline, then 12 weeks later. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline Neuropsychiatric Inventory Questionnaire subscale of caregiver distress at 12 weeks | The NPI-Q is a structured interview with a caregiver or qualified study partner (defined as having direct contact > 2 days/week) that evaluates both presence and severity of 12 neuropsychiatric features which include: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability, lability, apathy, aberrant motor behavior, night-time behavior, and appetite/ eating changes. A modification of the original NPI is the addition of a Caregiver Distress Scale for evaluating the psychological impact of neuropsychiatric symptoms reported to be present. For each feature the caregiver distress score ranges from 1-5 (No distress to extreme distress). The caregiver distress subscale score is the sum of the distress scores for each of the 12 features. Change in overall NPI-Q subscale of caregiver distress score which is the between baseline and at 12 weeks will be a secondary outcome measure. | Administered 2 times 1 baseline, then 12 weeks later. | 
| Change from Baseline Zarit Burden Interview Screening Version at 12 weeks | The Zarit Burden Interview (ZBI) Screening Version is a popular caregiver self-report measure used by many aging agencies, and originated as a 29-item questionnaire. The revised screening version contains 4 items and has been validated. Each item on the interview is a statement which the caregiver is asked to endorse using a 4-point scale. Response options range from 0 (Never) to 4 (Nearly Always). Change in overall ZBI score between baseline and at 12 weeks will be a secondary outcome measure. | Administered 2 times 1 baseline, then 12 weeks later. | 
| Change from Baseline Short Form Health Survey 12-Item at 12 weeks | The 12-Item Short Form Health Survey (SF-12) is a 12-item validated shortened version of the SF-36 and was designed to provide a health-related quality of life (HRQL) measure that was quick and easy to administer in large population studies. The SF-12 contains a subset of the 12 items from the SF-36 and information from this subset of questions is used to construct a physical and mental component summary score (PCS and MCS, respectively). Change in overall SF-12 score between baseline and at 12 weeks will be a secondary outcome measure. | Administered 2 times 1 baseline, then 12 weeks later. |