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

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

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

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Dietary supplement: Dietary Supplement:Aloe Vera with Crocus (saffron); Dietary supplement: Dietary Supplement:Aloe Vera (simple); Dietary supplement: Dietary Supplement:Mediterranean Diet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Thessaloniki
    • Thessaloníki, Thessaloniki, Greece, 54248
      • Greek Alzheimer's Association and Related Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Aloe Vera and Crocus; 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); Dietary Supplement:Aloe Vera with Crocus (saffron) with 1L of Aloe Vera with Crocus (saffron) 1 glass bottle per 15 days
PLACEBO_COMPARATOR: Aloe Vera; 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); Dietary Supplement:Aloe Vera (simple)with 1L of Aloe Vera 1 glass bottle per 15 days
OTHER: Mediterranean Diet; 50 patients Mediterranean dietary protocol Intervention:mediterranean diet	Dietary supplement: Dietary Supplement:Mediterranean Diet; Dietary Supplement:Mediterranean dietary protocol Intervention:mediterranean diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
NeuroImaging	Changes in brain Magnetic Resonance Imaging (MRI) 1.5 Tesla (brain atrophy)	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight in Kilograms	Changes in weight	baseline, 12 and 24 months
Height in Meters	Changes in Height	baseline, 12 and 24 months

Collaborators and Investigators

• Sponsor: Aristotle University Of Thessaloniki

Publications and helpful links

General Publications

• Tzekaki EE, Tsolaki M, Pantazaki AA, Geromichalos G, Lazarou E, Kozori M, Sinakos Z. Administration of the extra virgin olive oil (EVOO) in mild cognitive impairment (MCI) patients as a therapy for preventing the progress to AD. Hell J Nucl Med. 2019 Sep-Dec;22 Suppl 2:181.
• Tsolaki M, Karathanasi E, Lazarou I, Dovas K, Verykouki E, Karacostas A, Georgiadis K, Tsolaki A, Adam K, Kompatsiaris I, Sinakos Z. Efficacy and Safety of Crocus sativus L. in Patients with Mild Cognitive Impairment: One Year Single-Blind Randomized, with Parallel Groups, Clinical Trial. J Alzheimers Dis. 2016 Jul 27;54(1):129-33. doi: 10.3233/JAD-160304.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 17, 2017
• Primary Completion (ACTUAL): May 30, 2018
• Study Completion (ACTUAL): October 30, 2019

Study Registration Dates

• First Submitted: September 24, 2019
• First Submitted That Met QC Criteria: June 17, 2020
• First Posted (ACTUAL): June 18, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 22, 2020
• Last Update Submitted That Met QC Criteria: June 18, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Intervention; Mild Cognitive Impairment,; Aloe,; Crocus,
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 31b/17-05-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No