Magnesium L-Threonate for the Enhancement of Learning and Memory in People With Dementia

• ClinicalTrials.gov Identifier: NCT02210286
• Recruitment Status: Completed
• First Posted: August 6, 2014
• Results First Posted: February 2, 2021
• Last Update Posted: February 2, 2021
• Sponsor: Stanford University
• Collaborator: Magceutics, Inc.
• Information provided by (Responsible Party): Natalie Rasgon, Stanford University

Tracking Information

• First Submitted Date: August 1, 2014
• First Posted Date: August 6, 2014
• Results First Submitted Date: July 27, 2020
• Results First Posted Date: February 2, 2021
• Last Update Posted Date: February 2, 2021
• Study Start Date: July 2014
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 29, 2021)

• Change From Baseline in Cognitive Function [ Time Frame: Baseline and 6 months ]
  Neurocognitive assessment - Domain-specific composite scores for the four following cognitive areas include: 1a) Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-COG) (min: 0, max: 70, higher = better, units on a scale) 1b) Mini Mental Status Examination (MMSE) (min: 0, max : 30, higher = better, units on a scale) 1c) Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (min: 40, max: 160, higher = better, units on a scale) 1d) Wechsler Adult Intelligence Scale - Fourth edition (WAIS-IV) (min: 85 , max: 115, higher = better, units on a scale)
• Change From Baseline in Cognitive Function (DKEFS Color-Word Test) [ Time Frame: Baseline and 6 months ]
  1) Delis-Kaplan Executive Function System Color-Word Test (DKEFS, assesses executive functioning): no minimum or maximum set, higher is worse, total number of errors
• Change From Baseline in Cognitive Function (DKEFS - Trail 4) [ Time Frame: Baseline to 6 months ]
  This is a graphomotor test comprised of 5 conditions. Condition 4 (Number Letter Switching) is a measure of cognitive flexibility

Original Primary Outcome Measures (submitted: August 4, 2014)

Cognitive Function [ Time Frame: Baseline to 6 Month Follow Up ]

Neurocognitive assessment - Domain-specific composite scores for the four following cognitive areas include: 1a) memory composite score 1b) attention composite score 1c) learning composite score 1d) executive function composite score

Current Secondary Outcome Measures (submitted: January 29, 2021)

• Change From Baseline in CMRgl [ Time Frame: Baseline to Day 67 ]
  Brain imaging focusing on the following anatomical regions: medial temporal region (including hippocampus and entorhinal cortex), prefrontal cortex, parietotemporal cortex, posterior cingulate cortex. Increases in the summary index sROI have been shown to track AD-related CMRgl declines. We will be focusing on changes in the cerebral metabolic rate for glucose (CMRgl) from baseline to day 67.
• RBC Magnesium Chemistry [ Time Frame: Baseline and 6 months ]
  Magnesium (mg/dl) in red blood cells

Original Secondary Outcome Measures (submitted: August 4, 2014)

• FDG-PET [ Time Frame: Baseline to Day 67 ]
  Brain imaging focusing on the following anatomical regions: medial temporal region (including hippocampus andentorhinal cortex), prefrontal cortex, parietotemporal cortex, posterior cingulate cortex We will be focusing on two outcomes of interest: 2a) FDG-PET signal strength 2b) FDG-PET signal directionality
• RBC Magnesium chemistry [ Time Frame: Baseline to Day 60 ]
  Magnesium red blood cell levels

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Magnesium L-Threonate for the Enhancement of Learning and Memory in People With Dementia
• Official Title: The Use of Magnesium L-Threonate for the Enhancement of Learning and Memory in People With Mild to Moderate Dementia
• Brief Summary: The purpose of this study is to examine the effects of supplementing Magnesium L-Threonate in people with mild to moderate dementia. The investigators' goal is to understand whether Magnesium L-Threonate will be associated with improvement in memory and brain function.

Detailed Description

Emerging research on the effects of a novel magnesium compound of L-Threonic Acid Magnesium Salt (L-TAMS) containing Vitamins C and D on cognitive performance suggests that supplementation may benefit individuals with Alzheimer's disease (AD). This proof of concept will assess whether supplementation with Magtein (MGT), a constant release formula of Magnesium L-threonate, Vitamin C, and Vitamin D, is associated with changes in regional cerebral metabolism in elderly people with mild to moderate dementia.

This is an open-label, two-month trial consisting of 15-20 participants aged 60 and older with mild to moderate dementia. Subjects will receive 1,800 mg/day of MgT-1219 for a total of 60 days. They will be given neurocognitive testing, blood chemistries, and FDG-PET imaging at baseline, 60 days and more testing at 180 days to assess the acute effect of MgT-1219 on hippocampal and PFC-mediated executive function, attention, reasoning, and memory. Blood draws will be conducted prior to treatment initiation to assess kidney and liver function, complete blood count, fasting plasma insulin, and red blood cell magnesium.

Our outcome measures include a combination of neuropsychological testing and neuroimaging. These will be employed to measure changes in the degree of cognitive impairment within subjects over time, as well as between subjects in the intervention and control groups. FDG-PET imaging will be used to assess the degree of synaptic activity and density within subjects at different time points in the study. These measures will be supplemented by measures of, sleep quality, daytime sleepiness, depression, and activities of daily living.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Dementia
• Alzheimer's Disease

Intervention

Dietary Supplement: Magtein

Other Name: magnesium l-threonate

Study Arms

Experimental: Magtein

All participants will orally take a total of 1800 mg/day for 60 days. Oral administration includes two pills 2 hours before bed time and one pill in the morning, each pill containing 600 mg of MgT-1219.

Intervention: Dietary Supplement: Magtein

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 29, 2021): 17
• Original Estimated Enrollment (submitted: August 4, 2014): 20
• Actual Study Completion Date: July 2016
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• People of either gender > 60 years of age.
• Subject scores between 16 and 26 on the MMSE
• Subject or representative is willing to sign the consent for prior to enrollment into the study and to participate in all aspects of the study. Prospective subject must give verbal assent if unable to sign written consent.
• Adequate visual and auditory acuity to allow neuropsychological testing.
• Greater than 12 years of educational achievement, or a General Education Development certificate to allow adequate neuropsychological testing, and consistency of sample.
• Female subject is surgically sterile, post-menopausal or agrees to use an acceptable method of birth control.
• Subject agrees to stop taking any vitamins, minerals, or dietary/herbal supplements he/she is currently taking at least 7 days prior to randomization and agrees to not take any vitamins, minerals or dietary/herbal supplements other than the study product until after study completion.

Exclusion Criteria:

• Active heart disease
• Uncontrolled high blood pressure (≥ 140/90 mmHg)
• Renal or hepatic impairment/disease
• Type I diabetes
• Unstable thyroid disease
• Psychiatric disorder (hospitalized in the past year)
• History of drug or alcohol abuse.
• Immune disorder (such as HIV/AIDS)
• TIAs, carotid bruits, or verified lacunes
• Significant pulmonary disease
• Contraindication for a PET scan including those who have had a stroke or heart attack in the past 6 months, and those unable or unwilling to lie down for 1 hour.
• Any medical condition deemed exclusionary by the Principal Investigator (PI)
• History of cancer (except localized skin cancer without metastases or in situ cervical cancer) within 5 years prior to screening.
• Currently taking any medications that are known to interact with magnesium.
• Currently taking antibiotics as the study product may reduce the absorption of antibiotics. A washout period of 2 weeks is allowed.
• On an unstable dose of medication (defined as fewer than 90 days at the same dose).
• Currently taking any medication deemed exclusionary by PI.
• Allergy or sensitivity to any ingredient in the test product.
• Evidence of hepatic or renal dysfunction
• History of drug or alcohol abuse in the past 12 months.
• Pregnant , lactating, or planning to become pregnant during the study period.
• Subject has any condition or abnormality that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the study data.
• Subject is participating or has participated in another research study within 30 days prior to the screening visit.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02210286
• Other Study ID Numbers: 29329
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Natalie Rasgon, Stanford University
• Original Responsible Party: Same as current
• Current Study Sponsor: Stanford University
• Original Study Sponsor: Same as current
• Collaborators: Magceutics, Inc.

Investigators

• Principal Investigator: Natalie L Rasgon, MD, Ph.D; Stanford University

• PRS Account: Stanford University
• Verification Date: January 2021