Clinical trial NCT04641663: Multi-target Dietary Supplement Tolerability in an Aging Population (MTDSST)
Official title: Clinical Trial to Assess Tolerability and Availability of a Multi-target Dietary Supplement in an Aging Population
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Aging
Age-related Cognitive Decline
Keywords: Dietary Supplement
Aging
Safety
Tolerability
Lead sponsor: Northern Ontario School of Medicine
Sponsor class: OTHER
Collaborators: name: McMaster University
First posted: 2020-11-24
Enrollment: 70
Sex: ALL
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: participants will be taking either 60%, 80% or 100% of the recommended daily dose of the dietary supplement.
Primary purpose: TREATMENT

Brief summary: This study is being performed to determine if a multi-ingredient dietary supplement is safe and easy to take by healthy older adults. Participants will be required to take one of three different doses of the dietary supplement for 90 consecutive days and complete wellness surveys and a daily log while taking the supplement. Participants will also provide blood samples at the start of the study, after 30 days, and at the end of the study which will help determine how participants respond to the supplement.

Detailed description: Likely because of the highly complex nature of aging, there has been little success reducing age-related physical and cognitive deterioration. The predominant approach has been to manage emergent symptoms rather than mitigate the cellular mechanisms driving the degenerative processes underlying aging. Additionally, the multifaceted and complex etiology of aging makes it extremely difficult to provide effective interventions within current treatment paradigms. The medical community has established that preventative measures are the most effective means of slowing the progression of age-associated deterioration, however effective methods or interventions have not been established.

The Multi-Target Dietary Supplement (MTDS) was designed to simultaneously target and support the cellular processes implicated in the progression of the aging phenotype (oxidative stress, inflammatory processes, insulin resistance, and membrane and mitochondrial deterioration). The MTDS is unique in that it was specifically designed as a multi-target intervention to support the complex cellular perturbations associated with aging. Components of the formulation were chosen based on scientific consensus of documented effectiveness for one or more of the targeted processes, long-term evidence of safety, and synergistic or additive interactions between components.

In more than 20 years of pre-clinical research, the MTDS has demonstrated significant beneficial impacts in animal models of aging and age-associated disease. The MTDS has resulted in significant reductions in both acute and chronic oxidative stress, greatly improved mitochondrial function and efficiency, significantly reduced inflammatory processes and improved glucose metabolism. Signal transduction is normalized to youthful levels in aged animals, including key pathways implicated in aging (unpublished data). On a functional level, MTDS treatment has resulted in increased longevity of 10 to 28% in normal and accelerated aging phenotypes, respectively. Concomitant improvements in mobility, activity levels, muscle strength (exercise mimetic) and overall body condition in aged animals were observed. Dramatic reductions in the incidence of muscle wasting, arthritic processes, and cataracts were also observed. Sensory and cognitive acuity were protected and frequently enhanced in aged animals, with significant improvements in visual and olfactory function observed in a broad range of tasks. MTDS treatment has demonstrated profound sparing from age-related neuronal losses and corresponding protection of neurogenesis and enhanced synaptogenesis, resulting in dramatically improved cognition in aged animals. The quantity of data indicating MTDS efficacy in pre-clinical studies is considerable, however the effects of the MTDS in humans, although positive, remains anecdotal. This tolerability study is the critical first step to begin assessment of the efficacy of the MTDS in human populations. If even a portion of these protective effects of the MTDS are translatable from mice to humans, the positive impacts for the aging population and Ontario's healthcare system could be profound.

This is a multi-center, three-arm study designed to evaluate the safety of a dietary supplement at three dosing regimes for 90 days. Initially, 45 healthy volunteers will be randomly assigned to one of three dose regimes: 1) 100% of recommended daily dose (RDD), 2) 80% of recommended daily dose or 3) 60% of recommended daily dose. Dosing regimes are based on levels of the MORNING tablet doses, all groups will receive the full recommended dose for both EVENING and OMEGA doses. Written informed consent will be obtained and a medical history and health assessment will be performed. The investigator will determine whether the subject meets all inclusion and exclusion criteria. Health assessments will be made at baseline, 30 days and 90 days. Adverse events, concomitant medications, and product administration will be recorded throughout the study.

Compliance, safety, and tolerability parameters are the primary focus of this study; however the probability of serious adverse events is extremely low given the long safety history of safety of the vitamins and nutraceuticals that comprise the MTDS.

The primary objective is to evaluate the safety and tolerability of the MTDS regimen in terms of its administration at 3 dosing regimes for 90 consecutive days with respect to micronutrient levels, laboratory tests and adverse events.

The secondary objectives include:

1. monitoring compliance of taking the MTDS,
2. monitoring wellness as measured by the 36-Item Short Form Survey (SF-36) scale and daily journal, over the 90-day administration of the MTDS, and
3. to assess MTDS absorption through plasma micronutrient testing, at baseline, 30 days and 90 days following administration of the test agent.

Eligibility criteria: Inclusion Criteria:

1. Male or Female subjects ages of 45 and older.
2. Capable of providing informed consent
3. Patients currently taking fluconazole, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA) reductase inhibitors (i.e. "statin" drugs), or any other drug known to interfere with serum transaminase (i.e. liver enzymes), must have history of stable liver function test since first taking such drugs.
4. Patients who usually and customarily take dietary supplements, including vitamins, must undergo a two-week washout period

Exclusion Criteria:

1. Exposure to any investigational drug within 90 days of the beginning of this study
2. Known human immunodeficiency virus (HIV) seropositivity or Acquired Immunodeficiency Syndrome (AIDS); history of Hepatitis B (HBV), Hepatitis C (HCV) vital infection, unexplained elevated serum transaminase, or other hepatic disease. NOTE: HIV, HCV, and HBV testing will not be performed as part of screening.
3. History of cancer within the last 5 years, except for basal or squamous cell cancer.
4. Recent COVID-19 infection.
5. Allergy to fish (specifically sardines, anchovies or mackerel) or any of the investigational product components
6. Concomitant use, or use within less than a two-week period, of any other dietary supplement
7. Concomitant use of any drug known to interfere with laboratory measures such as:

   1. Niaspan (extended release niacin)
   2. Lamisil (terbinafine HCl)
   3. Chronic use of acetaminophen (\>1,500 mg/day) (occasional use for minor aches and pains is excluded from this restriction)
   4. Newly prescribed (\< 90days) HMG-CoA reductase inhibitors ("statin medications"), or patients currently on statin medications who have previously shown evidence of elevated serum transaminases
8. Currently diagnosed with multiple sclerosis, systemic lupus erythematosis, or other autoimmune disorders known to interfere with laboratory measures
9. History of alcoholism or drug abuse, unless it is determined that such past use would not influence laboratory measures (DSN4 criteria)
10. Any other active disease of a life-threatening nature or laboratory abnormality that, in the judgment of the investigator, may interfere with the interpretation, or increase risk of patient participation
11. Conditions that require nutritional therapy, such as:

    1. Pernicious anemia
    2. Iron-deficiency anemia
    3. Hartnup Disease or Pellagra
    4. Scurvy
    5. Beriberi-induced Endemic Neuritis

Primary outcomes:
measure: Number of Participants With Treatment-Related Adverse Events (AE) as Assessed by CTCAE v5.0
timeFrame: out to 90 days
measure: Hematocrit (%)
timeFrame: out to 90 days
measure: Hemoglobin (g/L)
timeFrame: out to 90 days
measure: Erythrocytes (10^12/L)
timeFrame: out to 90 days
measure: Leukocytes (10^9/L)
timeFrame: out to 90 days
measure: Basophils (10^3/uL)
timeFrame: out to 90 days
measure: Basophils/Leukocytes (%)
timeFrame: out to 90 days
measure: Eosinophils (10^9/L)
timeFrame: out to 90 days
measure: Eosinophils/Leukocytes (%)
timeFrame: out to 90 days
measure: Lymphocytes (10^9/L)
timeFrame: out to 90 days
measure: Lymphocytes/Leukocytes (%)
timeFrame: out to 90 days
measure: Monocytes (10^9/L)
timeFrame: out to 90 days
measure: Monocytes/Leukocytes (%)
timeFrame: out to 90 days
measure: Neutrophils (10^9/L)
timeFrame: out to 90 days
measure: Neutrophils/Leukocytes (%)
timeFrame: out to 90 days
measure: Platelet Count (10^9/L)
timeFrame: out to 90 days
measure: Serum Glucose (mmol/L)
timeFrame: out to 90 days
measure: Sodium (mmol/L)
timeFrame: out to 90 days
measure: Potassium (mmol/L)
timeFrame: out to 90 days
measure: Calcium (mmol/L)
timeFrame: out to 90 days
measure: Chloride (mmol/L)
timeFrame: out to 90 days
measure: Urea (mmol/L)
timeFrame: out to 90 days
measure: Creatinine (umol/L)
timeFrame: out to 90 days
measure: Urate (umol/L)
timeFrame: out to 90 days
measure: Albumin (g/L)
timeFrame: out to 90 days
measure: Alkaline Phosphatase (U/L)
timeFrame: out to 90 days
measure: Aspartate Phosphatase (U/L)
timeFrame: out to 90 days
measure: Alanine Transaminase (U/L)
timeFrame: out to 90 days
measure: Gamma Glutamyl Transpeptidase (U/L)
timeFrame: out to 90 days
measure: Total Bilirubin (umol/L)
timeFrame: out to 90 days
measure: Direct Bilirubin (umol/L)
timeFrame: out to 90 days
measure: Lactate Dehydrogenase (U/L)
timeFrame: out to 90 days
measure: High Sensitivity C-Reactive Protein (mg/L)
timeFrame: out to 90 days
Secondary outcomes:
measure: Vitamin A (mg/L)
timeFrame: out to 90 days
measure: Vitamin B1 (mg/L)
timeFrame: out to 90 days
measure: Vitamin B2 (mg/L)
timeFrame: out to 90 days
measure: Vitamin B3 (mg/L)
timeFrame: out to 90 days
measure: Vitamin B6 (mg/L)
timeFrame: out to 90 days
measure: Vitamin B12 (mg/L)
timeFrame: out to 90 days
measure: Biotin (mg/L)
timeFrame: out to 90 days
measure: Folate (mg/L)
timeFrame: out to 90 days
measure: Pantothenate (mg/L)
timeFrame: out to 90 days
measure: Vitamin C (mg/L)
timeFrame: out to 90 days
measure: Vitamin D3 (mg/L)
timeFrame: out to 90 days
measure: Vitamin K2 (mg/L)
timeFrame: out to 90 days
measure: Magnesium (mg/L)
timeFrame: out to 90 days
measure: Manganese (mg/L)
timeFrame: out to 90 days
measure: Zinc (mg/L)
timeFrame: out to 90 days
measure: Copper (mg/L)
timeFrame: out to 90 days
measure: Alpha Lipoic Acid (mg/L)
timeFrame: out to 90 days
measure: Glutamine (mg/L)
timeFrame: out to 90 days
measure: Glutathione (mg/L)
timeFrame: out to 90 days
measure: Carnitine (mg/L)
timeFrame: out to 90 days
measure: Choline (mg/L)
timeFrame: out to 90 days
measure: Inositol (mg/L)
timeFrame: out to 90 days
measure: Coenzyme Q10 (mg/L)
timeFrame: out to 90 days
measure: 36-Item Short Form Survey (SF-36)
timeFrame: up to 90 days
Other outcomes:
Locations:
city: Elliot Lake
country: Canada
facility: Northern Ontario School of Medicine - Elliot Lake site
state: Ontario
city: Hamilton
country: Canada
facility: McMaster University - Behavioural Neurosciences
state: Ontario
Study officials:
affiliation: Northern Ontario School of Medicine
name: Douglas Boreham, PhD
role: PRINCIPAL_INVESTIGATOR
References: