Comparative Effects of a2 Skim Milk on Mild Cognitive Impairment in Older Adults

Comparing the Effect of Powdered Skim Milk Containing A2 β-casein Only Versus Conventional Powdered Skim Milk Containing A1 and A2 β-caseins on Mild Cognitive Impairment in Older Adults: a Double-blind, Randomized, Controlled Trial

The aim of the study is to compare the effects of powdered skim milk containing A2 β-casein only versus conventional powdered skim milk containing A1 and A2 β-casein milk on cognition, inflammation, and dietary intake in adults aged 65-75 years.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment; Adults
• Intervention / Treatment: Other: a2Milk skim milk powder; Other: Yili skim milk powder

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Tianjin, China
    • General Hospital of Tianjin Medical University
  • Tianjin, China
    • The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 75 years (Older Adult)
• Accepts Healthy Volunteers: No

Description

For inclusion in the study, participants must meet all of the following criteria:

1. Adults aged 65-75 years;
2. Complaint of memory loss for more than 6 months;
3. Base on the Chinese version of Mini Mental State Examination (MMSE), cognitive ability score is lower than the standard cut-off value according to age and education levels: MMSE score≤ 17 points if years of education is 0 year; ≤ 20 points if 6 years or less of education; ≤ 24 points if more than 6 years of education
4. Living and social functions are reduced: activities of daily living (ADL) score ≤18;
5. Not meeting the diagnostic criteria for dementia (Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition), Alzheimer Disease (National Stroke Institute for Neuropathic Speech Disorders and Association for Alzheimer Disease and Related Disorders); no mental disorder, brain damage, or other physical disorders that can lead to cognitive impairment.
6. Agreed not to participate in another interventional clinical research study during the present study;
7. Signed informed consent

Participants must be excluded from the study if they meet any of the following criteria:

1. <65 years; or >75 years
2. Neurological examination showed focal signs of central nervous system disorder such as hemiplegia, dysesthesia, aphasia; history of cerebrovascular diseases (including hemorrhagic and ischemic types), internal brain trauma or fracture;
3. Asthmatic bronchitis, severe hypertension, angina and severe infection;
4. Mental disorders such as depression and anxiety; endocrine system diseases (such as hyperthyroidism, hypothyroidism, systemic lupus erythematosus, rheumatoid arthritis);
5. Newly diagnosed, progressing or advanced tumors;
6. Visual, reading, hearing impairment or language communication difficulties that significantly affect cognitive function tests;
7. History of alcohol dependence and abuse of psychoactive substances (e.g., antipsychotics, benzodiazepines, cholinesterase inhibitors, sedatives), or use of drugs that affect cognitive function;
8. Neurological diseases (e.g. Parkinson's disease, epilepsy);
9. Antibiotic treatment in previous 2 weeks;
10. Administered immunosuppressive drugs in the 4-weeks preceding screening;
11. Allergy to milk or dairy;
12. Diagnosed lactose intolerance;
13. Other diseases that investigators judged as unsuitable to participate the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: a2 Group; The group consuming a2Milk skim milk powder (1L) containing A2 β-casein only	Other: a2Milk skim milk powder; a2Milk skim milk powder (1L) containing A2 β-casein only; Other Names: Treatment group
Placebo Comparator: Control Group; The group consuming Yili skim milk powder (1L) containing A1 and A2 β-caseins	Other: Yili skim milk powder; Yili skim milk powder (1L) containing A1 and A2 β-caseins; Other Names: Control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of Subtle Cognitive Impairment Test (SCIT) at Visit 2 and Visit 4 compared to baseline	Record responding time and speed on the SCIT test	Visit 2 (14 days after baseline); Visit 4 (90 days after baseline); baseline (14 days after enrolment)
Changes of serum glutathione (GSH) at Visit 2 and Visit 4 compared to baseline	Record serum glutathione (GSH) (µmol/L) as an anti-oxidation marker	Visit 2 (14 days after baseline); Visit 4 (90 days after baseline); baseline (14 days after enrolment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of short-chain fatty acids at Visit 2, 3, and 4 compared to baseline	Record short-chain fatty acids (mg/g) as a faecal marker of inflammation	Visit 2 (14 days after baseline); Visit 3 (28 days after baseline); Visit 4 (90 days after baseline); baseline (14 days after enrolment)
Changes of quality of life at Visit 4 compared to baseline	Record Healthy Brain Ageing - Functional Assessment Questionnaire via patient self-report as a quality of life measure	Visit 4 (90 days after baseline); baseline (14 days after enrolment)
Changes of C-reactive protein at Visit 2 and 4 compared to baseline	Record C-reactive protein (mg/L) as a blood marker of inflammation	Visit 2 (14 days after baseline); Visit 4 (90 days after baseline); baseline (14 days after enrolment)

Collaborators and Investigators

• Sponsor: a2 Milk Company Ltd.
• Collaborators: First Teaching Hospital of Tianjin University of Traditional Chinese Medicine; General Hospital of Tianjin Medical University; Edanz Group Japan Ltd; Beijing Esmile Technology Co. Ltd.
• Investigators: Principal Investigator: Keming Zhang, MD, The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2023
• Primary Completion (Actual): October 13, 2023
• Study Completion (Actual): October 13, 2023

Study Registration Dates

• First Submitted: February 14, 2023
• First Submitted That Met QC Criteria: February 14, 2023
• First Posted (Actual): February 23, 2023

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: A2MC-G190549358

Drug and device information, study documents

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