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Trial registered on ANZCTR


Registration number
ACTRN12622001576718
Ethics application status
Approved
Date submitted
3/11/2022
Date registered
20/12/2022
Date last updated
18/08/2024
Date data sharing statement initially provided
20/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of a biofactor-combination on cognitive function in mildly cognitive impaired patients - a randomized, double-blind, placebo-controlled trial
Scientific title
Effects of a biofactor-combination on cognitive function in mildly cognitive
impaired patients - a randomized, phase IIa, double-blind, placebo-controlled
pilot-trial
Secondary ID [1] 308053 0
WOE-Cocktail-01
Universal Trial Number (UTN)
U1111-1283-8813
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild Cognitive Impairment 327746 0
Condition category
Condition code
Neurological 324817 324817 0 0
Other neurological disorders
Neurological 324962 324962 0 0
Dementias
Neurological 325055 325055 0 0
Alzheimer's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: The active investigational medicinal product is a bio-factor combination containing well established vitamins and minerals provided as a combination of 5 medicinal products with marketing authorization in Europe. The treatment contains B-Vitamins (1-300 mg), Vitamin D (50 ug) and Magnesium (196.8 mg) within the approved dosages of the respective drugs.

Patients will be asked to return all remaining investigational medical product and the empty packaging for used investigational medical product at Visits 3, 4, and 5. Based on the back counted tablets, the compliance will be calculated. All participants will be given a patient diary to help remind them to take their treatment and to document daily intake. Patients treatment compliance will be monitored through regular phone and/or email contact (at least every 2 weeks). Blood levels of respective vitamins will be evaluated for evaluation of compliance after database closure.

11 tablets to be taken by mouth daily; 3 in the morning, 5 at noon and 3 in the evening for 168 days. The morning and evening sachets will contain magnesium or the corresponding placebo. The noon sachet will contain B-vitamins and tablets with vitamin D or the corresponding placebos.
Intervention code [1] 324501 0
Treatment: Drugs
Intervention code [2] 324604 0
Prevention
Comparator / control treatment
Placebo Comparator: for each active investigational medical product a corresponding placebo with the same appearance will be available. Placebo tablets are of same composition as the active tablets, just without the active ingredient. The main inactive ingredients include: glucose, lactose, sucrose, gelatine and corn starch. 11 placebo tablets will be taken daily by mouth for 168 days.
Control group
Placebo

Outcomes
Primary outcome [1] 332635 0
To assess the effect of the the investigational medicinal products on symptoms of MCI.
-Any changes in Error Score on the Paired Associates Learning task (PAL) of the Cambridge Neuropsychological Test Automated Battery (CANTAB) at day 168.
Timepoint [1] 332635 0
Day 168 post-intervention commencement
Secondary outcome [1] 414647 0
To assess the effects of the investigational products on surrogate markers of cognitive impairment
- Any changes in the Error Score on the PAL of CANTAB
Timepoint [1] 414647 0
At days 42 and 84 post-intervention commencement
Secondary outcome [2] 414648 0
To assess the effects of the investigational products on surrogate markers of cognitive impairment
- Cognitive performance as assessed by other CANTAB tests, including Spatial Working Memory (SWM)
Timepoint [2] 414648 0
At 42 days, 84 days and 168 days post-intervention commencement
Secondary outcome [3] 414649 0
To assess the effects of the investigational products on surrogate markers of cognitive impairment
- The Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog)
Timepoint [3] 414649 0
At day 168 post-intervention commencement
Secondary outcome [4] 414650 0
To assess the influence of supplementation with the Investigational Medical Product on vitamin and mineral blood levels
- Level of B-Vitamins
Timepoint [4] 414650 0
Day 168 post-intervention commencement
Secondary outcome [5] 415751 0
To assess the influence of supplementation with the Investigational Medical Product on vitamin and mineral blood levels
- Level of cholecalciferol
Timepoint [5] 415751 0
Day 168 post-intervention commencement
Secondary outcome [6] 415752 0
To assess the influence of supplementation with the Investigational Medical Product on vitamin and mineral blood levels
- Level of magnesium
Timepoint [6] 415752 0
Day 168 post-intervention commencement
Secondary outcome [7] 415753 0
Subjective evaluation of efficacy by patient
- efficacy assessed by responses to a study-specific questionnaire
Timepoint [7] 415753 0
Day 168 post-intervention commencement
Secondary outcome [8] 415754 0
Safety evaluation
- Rate of adverse events in the two groups
Adverse events will be assessed by short clinical interview and rated for severity, relatedness and seriousness. Examples of known/possible adverse events include gastrointestinal complaints, hypersensitivity reactions and changes to mood and sleep.
Timepoint [8] 415754 0
Day 168 post-intervention commencement
Secondary outcome [9] 415755 0
Safety evaluation
- Changes in vital signs (Blood pressure and heart rate)
Brachial Blood pressure and heart rate measurements will be calculated using the OMRON HEM-907 automated blood pressure machine.
Timepoint [9] 415755 0
At 42 days, 84 days and 168 days post-intervention commencement
Secondary outcome [10] 415756 0
Safety evaluation
- changes in safety blood markers
Biochemistry tests that will be used to asses safety will include: sodium, potassium, calcium, phosphate, chloride, bicarbonate, creatinine, urea, uric acid, glucose, albumin, total bilirubin, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, total protein, globulin, creatine kinase (CK), C-reactive protein (CRP), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), aspartate transferase (AST) and Alanine transaminase (ALT).
Haematology tests that will be used to asses safety will include: hemoglobin, hematocrit, red blood cell count (RBC), white blood cell count (WBC), mean cell volume (MCV), mean corpuscular hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), platelet count and differential white blood cell count.
Timepoint [10] 415756 0
At 42 days, 84 days and 168 days post-intervention commencement
Secondary outcome [11] 415757 0
- Depression Anxiety and Stress Questionnaire (DASS)
Timepoint [11] 415757 0
Day 168 post-intervention commencement

Eligibility
Key inclusion criteria
• Men and women 60 years or older
• Subjectively felt memory complaints that are defined as worrisome by the subject
• Impairment in one or more cognitive domains, identified as the person scoring >1 standard deviation below the normative data for their age and/ or estimated levels of
premorbid functioning as identified by a neuropsychological screening battery
• Montreal Cognitive Assessment (MoCA) score equal to or greater than 17
• Geriatric Depression Scale (short form) score equal to or less than 10
• Functional Activities Questionnaire score equal to or less than 6
• Preserved activities of daily living and an absence of dementia
• Able to comply with all procedures linked to this trial, including the intake of all daily doses of investigational medical product
Minimum age
60 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Any ongoing concomitant disease that may influence cognitive functions
• Under treatment with drugs or supplements that interfere with cognitive functions within the two months before randomisation
• Any previous treatment with acetylcholinesterase inhibitors or other AD disease modifying drugs
• Any contraindication to the use of the investigational medical product
• Significant or insufficiently treated hepatic, renal, respiratory, cardiovascular, metabolic, oncological, immunological or hormonal disorders
• Major cardiovascular event, such as a myocardial infarction or stroke, in the last 12 months before randomisation
• Carotid stents or severe stenosis
• Any other existing medical conditions likely to affect the study measures (as judged by the clinical investigator)
• Uncontrolled hypertension (systolic blood pressure (SBP) >160 mm Hg, diastolic blood pressure (DBP) >100 mm Hg)
• BMI equal to or greater than 40kg/m2
• History of allergy/hypersensitivity to drugs or to the investigational medical product
• Treatment with any drugs or food supplements containing vitamins and minerals in the investigational medical product must be stopped 2 months before randomisation
• Current smokers, or having stopped smoking < 6 months before randomisation
• Use of recreational drugs
• Participation in another clinical study within the 2 months preceding randomisation
• Not able to comply with the study requirements
• not willing or able to sign the informed consent

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation concealment will be done via numbered containers.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomized to the intervention or control group centrally according to a computer-generated randomisation code.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Baseline characteristics will be compared between groups using a Fisher test for binary variables, Analysis of Variance (ANOVA) for normally distributed continuous variables and Mann-Whitney procedures for all other categorical or continuous variables, respectively.

Primary outcome parameter is Errors on the Paired Associates Learning task (PAL) of the Cambridge Neuropsychological Test Automated Battery (CANTAB). The number of Errors at week 24 compared to baseline will be summarized by usual methods (calculation of mean, median, 95% confidence intervals of the mean) and analyzed descriptively and compared between groups using Poisson ANOVA analysis adjusted for appropriate control variables (age, highest level of education , etc.).

Secondary outcome measures, as well as the exploratory endpoints will be analysed descriptively. Summary tables will be presented separately for each group. Between groups comparisons will be performed with adequate statistical tests (e.g., repeated measurement analyses examining the course of variables over time, Wilcoxon tests for continuous and Fisher’s exact tests for binary outcome measures). The corresponding effect size measures and confidence intervals will also be presented.

The primary outcome variable will be the change in Paired Associates Learning (PAL) errors at 24 weeks from Baseline. We expect a moderate effect size for PAL change over 6 months of supplementation. This being a pilot study, however, a formal power analysis is not appropriate. The effect size from PAL (or possibly other measures) will be used to formally power a further larger study. Based on studies with similar biofactors and endpoints with comparable sensitivity, a sample size of 20 completers per group should be sufficient to identify a statistical signal

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/06/2023
Actual
21/05/2024
Date of last participant enrolment
Anticipated
1/03/2025
Actual
Date of last data collection
Anticipated
1/08/2025
Actual
Sample size
Target
40
Accrual to date
12
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 38590 0
3122 - Hawthorn

Funding & Sponsors
Funding source category [1] 312308 0
Commercial sector/Industry
Name [1] 312308 0
Wörwag Pharma GmbH & Co. KG
Country [1] 312308 0
Germany
Primary sponsor type
Commercial sector/Industry
Name
Wörwag Pharma GmbH & Co. KG
Address
Flugfeld-Allee 24,
71034 Böblingen, Germany
Country
Germany
Secondary sponsor category [1] 313988 0
University
Name [1] 313988 0
Swinburne University Of Technology
Address [1] 313988 0
John St, Hawthorn VIC 3122
Country [1] 313988 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311677 0
Swinburne University Ethics Committee
Ethics committee address [1] 311677 0
Ethics committee country [1] 311677 0
Australia
Date submitted for ethics approval [1] 311677 0
03/01/2023
Approval date [1] 311677 0
24/03/2023
Ethics approval number [1] 311677 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121962 0
Prof Andrew Pipingas
Address 121962 0
Swinburne University of Technology
John Street, Hawthorn
Victoria
3122
Country 121962 0
Australia
Phone 121962 0
+61 3 9214 5215
Fax 121962 0
Email 121962 0
[email protected]
Contact person for public queries
Name 121963 0
Rebecca King
Address 121963 0
Swinburne University of Technology
John Street, Hawthorn
Victoria
3122
Country 121963 0
Australia
Phone 121963 0
+61 3 9214 5861
Fax 121963 0
Email 121963 0
[email protected]
Contact person for scientific queries
Name 121964 0
Andrew Scholey
Address 121964 0
Swinburne University of Technology
John Street, Hawthorn
Victoria
3122
Country 121964 0
Australia
Phone 121964 0
+61 43858 7523
Fax 121964 0
Email 121964 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.