Management of Mild Cognitive Impairment Patients With Aloe and Crocus - BALSAM

Study Overview
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Brief Summary
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There is accumulating evidence suggesting that Aloe vera and Crocus (saffron) may have a positive impact on conditions involving cognitive deficits, such as Mild Cognitive Impairment (MCI) and AD. More specifically, aloe vera gel contains powerful antioxidants, which belong to a large family of substances known as polyphenols. Aloe has also been proven to possess cholinergic and cognitive enhancing capabilities. Crocus is deeper studied and it shows promising results in neuroprotection against AD through various suggested mechanisms, such as the enhancement of amyloid-beta clearance in the brain and the inhibition of neurofibrillary tangles formation. For this reason, it would be interesting to study the effects of combination of Aloe Vera and Crocus . The aim of the study is to evaluate the beneficial effect of Aloe Vera and Crocus (saffron) in comparison with Aloe (simple)on patients diagnosed with mild cognitive impairment MCI. Study Type: Interventional Study Design: Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention

Detailed Description
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OBJECTIVES OF THE TRIAL The objectives of this study are: To investigate the efficacy of Aloe Vera and Crocus as a disease course modifying treatment for MCI in a phase III double-blind placebo-controlled study. To investigate the effects in objective measurements in patients with MCI. STUDY DESIGN This is a Greek, randomised, double-blind, placebo-controlled study group of compared Aloe Vera and Crocus with placebo. Qualifying patients will be randomly assigned to receive 45 mL of Aloe Vera and Crocus or placebo (ALOE) or mediterranean dietary protocol on a daily basis for 24 months. Patients undergo assessments at baseline,12 and 24 months +/- 7 days after beginning of the treatment. Duration The total study duration will be 36 months. Patients will receive study medication for 24 months.The recruitment will be about 6 months and the statistics and the preparation of the paper other 6 months. Number of Subjects One hundred fifty (150) subjects total will be enrolled. ; Fifty (50) in the experimental group (Aloe Vera with Crocus); Fifty (50) in the Control Group 1(Aloe) and fifty (50) in control Group 2(same dietary habits-mediterranean dietary protocol). Patient Eligibility Screening Form (ESF) An eligibility form documenting the patient's fulfilment of the entry criteria will be completed by the assessor. The following information will be included in the ESF: Patient identification: Initials (First initial of first name and First initial of surname), date of birth and Patient Identification Number. Eligibility Screening; Checklist of inclusion and exclusion criteria Eligibility Statement; for patients found to be ineligible, the reason for ineligibility must be stated Written informed consent will be obtained from the subject . The informed consent form must be co-signed by the physician. The nature of the study and the potential risks associated with the trial will be explained to all subject candidates and their responsible informants. Signature and date: the ESF may be completed by an assessor but it is required that the principal investigator/study clinician sign and date the ESF to verify eligibility of the patient for inclusion.

Official Title
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Randomized, Double Blind, Placebo Controlled Prospective Study, to Evaluate the Effect of Aloe Vera and Crocus in Patiens With Mild Cognitive Impairment

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Dietary Supplement: Dietary Supplement:Aloe Vera with Crocus (saffron)
* Dietary Supplement: Dietary Supplement:Aloe Vera (simple)
* Dietary Supplement: Dietary Supplement:Mediterranean Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Memory Complaints Abnormal memory function documented by scoring 1 SD below the age-adjusted mean on the Logical Memory II subscale, (Delayed Paragraph Recall) from the Wechsler Memory Scale-R. MMSE 24-30 CDR(sum of boxes) >= 0,5 Diagnosis: Mild Cognitive Impairment (amnestic plus multi-domain) Geriatric Depression Scale (GDS) <6 Hachinski Modified Ischemic scale <= 4 Stability of Permitted Medications for 4 weeks Years of education: >= 5 Proficient language fluency Compliance Exclusion Criteria: Visual and auditory acuity inadequate for neuropsychological testing Enrollment in other trials or studies not compatible with MICOIL History of significant neurological or psychiatric illnesses or presence of other diseases precluding enrollment. Use of forbidden medications (listed below) Ferromagnetic implants and devices (including implants or devices held in place by sutures, granulation or ingrowth of tissue, fixation devices, or by other means) not eligible for MRI scanning. Brain malformation or other conditions that may complicate lumbar puncture Excluded Medication: Antidepressants with anti-cholinergic properties. Regular use of narcotic analgesics (>2 doses per week) within 4 weeks of screening. Use of neuroleptics with anti-cholinergic properties (e.g., chlorpromazine, thioridazine) within 4 weeks of screening. Chronic use of other medications with significant central nervous system anticholinergic activity within 4 weeks of screening (e.g., diphenhydramine). Use of Anti-Parkinsonian medications (including Sinemet, amantadine, bromocriptine, pergolide, selegeline) within 4 weeks of screening. Participation in any other investigational drug study within 4 weeks of screening (individuals may not participate in any drug study while participating in this protocol).

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 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: Single (Participant)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aloe Vera and Crocus<br>50 patients Aloe Vera and Crocus (saffron) 1L, 1 bottle per 15 days. Dietary Supplement: Aloe Vera and Crocus (saffron) in a glass bottle Intervention: Dietary Supplement: Aloe Vera and Crocus (saffron) in a glass bottle 1L, per 15 days. | Dietary Supplement: Dietary Supplement:Aloe Vera with Crocus (saffron)<br>* Dietary Supplement:Aloe Vera with Crocus (saffron) with 1L of Aloe Vera with Crocus (saffron) 1 glass bottle per 15 days<br>|
| Placebo Comparator: Aloe Vera<br>50 patients Aloe Vera (simple) in a glass bottle 1L, 1 bottle per 15 days. Dietary Supplement: Aloe Vera (simple) in a glass bottle Intervention: Dietary Supplement: Aloe Vera (simple) in a glass bottle in a glass bottle 1L, per 15 days. | Dietary Supplement: Dietary Supplement:Aloe Vera (simple)<br>* Dietary Supplement:Aloe Vera (simple)with 1L of Aloe Vera 1 glass bottle per 15 days<br>|
| Other: Mediterranean Diet<br>50 patients Mediterranean dietary protocol Intervention:mediterranean diet | Dietary Supplement: Dietary Supplement:Mediterranean Diet<br>* Dietary Supplement:Mediterranean dietary protocol Intervention:mediterranean diet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychological Assessment- Measurements to Assess General Cognitive Function. | Changes in Mini-Mental State Examination (MMSE) score | baseline, 12 and 24 months | 
| FUCAS-Measurements to Assess Daily Functionality | Changes in Functional cognitive assessment scale (FUCAS) score score scale:0-42,cut offs:<42 | baseline, 12 and 24 months | 
| Letter & Category Fluency Test- Measurement to Assess Verbal Fluency and Learning | Changes in the Letter & Category Fluency Test | baseline, 12 and 24 months | 
| CDR- Measurements to Assess General Cognitive Function | Changes in Global Clinical Dementia Rating (CDR) score (sum of boxes) | baseline, 12 and 24 months | 
| MoCA- Measurements to Assess General Cognitive Function | Changes in Montreal Cognitive Assessment (MoCA) | baseline, 12 and 24 months | 
| Clock Drawing test- Measurements to Assess General Cognitive Function | Changes in the Clock Drawing test | baseline, 12 and 24 months | 
| Logical Memory test- Measurements to Assess General Cognitive Function | Changes in the Logical Memory test | baseline, 12 and 24 months | 
| Digit Span Forward & Backward test- Measurements to Assess General Cognitive Function | Changes in the Digit Span Forward & Backward test | baseline, 12 and 24 months | 
| WAIS-R Digit Symbol- Measurements to Assess General Cognitive Function | Changes in the WAIS-R Digit Symbol Substitution Test | baseline, 12 and 24 months | 
| TMT part A and B- Measurements to Assess General Cognitive Function | Changes in the Trail Making Test | baseline, 12 and 24 months | 
| ADASCog-Measurements to Assess Daily Functionality | Changes in Alzheimer's Disease Assessment Scale-Cognitive (ADASCog) | baseline, 12 and 24 months | 
| Functional Rating Scale for Dementia-Measurements to Assess Daily Functionality | Changes in Functional Rating Scale for Dementia (FRSSD) | baseline, 12 and 24 months | 
| Auditory Verbal Learning Test- Measurement to Assess Verbal Fluency and Learning | Changes in the Auditory Verbal Learning Test | baseline, 12 and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NeuroImaging | Changes in brain Magnetic Resonance Imaging (MRI) 1.5 Tesla (brain atrophy) | baseline, 12 and 24 months | 
| CSF - beta amyloid | Changes in mean values on high sensitivity beta-amyloid 1-42 protein | baseline, 12 and 24 months | 
| CSF TAU-protein | Changes in mean values on TAU-protein in cerebrospinal fluid | baseline, 12 and 24 months | 
| Electroencephalography recording | Changes in Event-Related Potential (ERP) (oddball paradigm, auditory ERPs) Electroencephalography recording Changes in Electroencephalography (EEG), resting state. The device records brain signals through 57 electrodes, 2 reference electrodes attached to the earlobes, and a ground electrode placed at a left anterior position | baseline, 12 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crocus,, Intervention, Mild Cognitive Impairment,, Aloe,