To Evaluate the Efficacy and Safety of NMN as an Anti-ageing Supplement in Middle Aged and Older (40-65 Years) Adults
Condition: Aging
Study type: Interventional

Summary: 
      It will be a two-part study. Part I will be six arms; randomized, double blind, parallel
      design, placebo-controlled dose ranging study. Part II will be open-label single dose study
      at the highest dose.

      A total of 90 Subjects (Part 1 & Part 2) will be enrolled in the study. The Part 1 group
      subjects (80 Subjects) shall be randomly distributed between the six arms, i.e. 20 Subjects
      each in IP arms, and 7, 7 and 6 subjects in corresponding placebo arms.

      All Part 2 Group subjects (10 Subjects) will be assigned into the cluster where all receive
      the maximum NMN dose (900 mg)
    

Detailed description: 
      It will be a two-part study. Part I will be six arms; randomized, double blind, parallel
      design, placebo-controlled dose ranging study. Part II will be open-label single dose study
      at the highest dose.

      Total number of Subjects is N = 90 (Part 1 & Part 2) Part I: six arms Arm A = 300 mg NMN
      supplement (n = 20) Arm B = Placebo of 300 mg NMN supplement (n = 07) Arm C = 600 mg NMN
      supplement (n = 20) Arm D = Placebo of 600 mg NMN supplement (n = 07) Arm E = 900 mg NMN
      supplement (n = 20) Arm F = Placebo of 900 mg NMN supplement (n = 06) Part II 900 mg NMN
      supplement (n = 10) Duration of Protocol Therapy = 60 Days Study Population= Middle aged or
      older male or female subjects (40-65 years)

      The duration of each subject's participation in the study will be of 60 days. Scheduled study
      visits will include:

        -  Visit 1 (Screening, Day -4)

        -  Visit 2 (Baseline/Randomization visit, Day 1)

        -  Visit 3 (Day 30).

        -  Visit 4 (End of study, Day 60) A window (± 2 days) will be considered acceptable for
           each scheduled visit following the baseline visit.

      During Visit 1 (Screening), informed consent will be obtained before any study procedures
      take place. After subject has consented, medical history will then be documented, including
      the concomitant medications (if any). Physical examination and ECG will be carried out for
      all subjects. Subjects' vital signs will be recorded along with pulse pressure (PP). Their
      laboratory investigations like Hematology, Clinical chemistry and Urinalysis will be done.
      They will be symptomatically assessed for COVID-19. They shall undergo the screening
      procedure by inclusion and exclusion criteria. Subject's demography data will be collected.
      They will be given instructions for the next visit.

      At Visit 2 (Day 1, Baseline visit), eligibility confirmation will be done, and each enrolled
      subject will be randomly assigned in double-blind fashion, in 1:1 ratio to the test product
      or the Placebo or to the maximum dose group (Part 2 subjects). Blinded investigational
      product will be dispensed to subjects for Part 1 who meet all the inclusion and none of the
      exclusion criteria. Part 2 group subjects will be dispensed with maximum dose of NMN (900mg)
      without any blinding. Subjects will be instructed to take two to six capsules (depending on
      thegroups that the subjects fall under) of the either placebo or NMN once a day with ambient
      temperature water before breakfast. They shall be recording the dosing details in subject
      diaries. The Investigational Product will be taken by the subject at home right from the
      first dose. Subjects will be evaluated through SF-36 questionnaire for their health. They
      will be required to answer the list of questions pertaining to their health. (PI, CRC or site
      staff will fill SF-36 questionnaire in visit 2, 3 and 4 by asking the subject). All the
      baseline assessments for efficacy will be performed.

      At visit 3 (Day 30) and visit 4 (Day 60), subjects will return to the clinic to review and
      collect subjects' diaries, safety data and medication reconciliation. Efficacy and safety
      assessments will be done at both the visits.

      Subjects will be asked to bring their subject diaries and used/unused Investigational Product
      every time they visit the site(empty bottles in case of used IP). Enough quantity of
      Investigational Product will be dispensed every visit. Subjects' vital signs will be recorded
      along with pulse pressure (PP) at all visits. Adverse event assessment and concomitant
      assessment will be done at each visit along with compliance with study supplement
      administration.

      End points:

      Primary efficacy endpoints (Part I ) Blood cellular NAD/NADH concentration in serum [ Time
      Frame: Baseline, 1 month and 2 Months] Six minutes walking endurance test [ Time Frame:
      Baseline, 1 month and 2 Months] SF-36 questionnaire [ Time Frame: Baseline, 1 month and 2
      Months]

      Secondary endpoints :

        1. To compare the safety of NMN versus placebo [ Time Frame: Baseline to 2 Months]

        2. Monitoring and documentation of number and type of adverse events including changes on
           laboratory parameter (blood chemistry, lipid profile, LFT and RFT)

        3. To compare the tolerability of NMN versus placebo [ Time Frame: Baseline to 2 Months]
           Tolerability: Number of participants that dropout due to adverse events including lab
           values

        4. Monitoring and documentation of subject dropout due to adverse events

        5. To compare the safety of the different NMN doses [ Time Frame: Baseline to 2 Months]

        6. Monitoring and documentation of number and type of adverse events including changes on
           laboratory parameter (blood chemistry, lipid profile, LFT and RFT)

        7. To compare the tolerability different NMN doses [ Time Frame: Baseline to 2 Months]
           Tolerability: Number of participants that dropout due to adverse events including lab
           values Monitoring and documentation of subject

      Exploratory endpoints :

        1. BMI

        2. HOMA (Homeostatic model assessment) Biological Age using Aging.Ai 3.0 calculator [ Time
           Frame: Baseline to 2 Months]

      Primary Endpoints : (Part II)

      Evaluation will include the following parameters:

        1. Telomerase test results [ Time Frame: Baseline and 2 Months]

        2. SF-36 questionnaire [ Time Frame: Baseline and 2 Months]

      Secondary endpoint:

        1. Safety of NMN [ Time Frame: Baseline to 2 Months]

        2. Monitoring and documentation of number and type of adverse events including changes on
           laboratory parameter (blood chemistry, lipid profile, LFT and RFT, CEA test)
    

Intervention name(s): Nicotinamide Mononucleotide; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor in all living cells involved in fundamental biological processes. Depletion in the levels of NAD+ is associated with traits of aging, many age-related diseases like cancer, metabolic disorders and neurological disorders. Evidence stemming from recent studies have unveiled numerous roles of NAD+ metabolism on aging and longevity and delaying the progression of age-related diseases; Rice flour in white capsule resembling NMN
Intervention MeSH terms: Niacinamide; Niacin; Nicotinic Acids
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Nicotinamide Mononucleotide (NMN); Anti Ageing; Telomerase