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Trial record 2 of 6 for:    chromadex

Nicotinamide Riboside in Hospitalized Patients

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ClinicalTrials.gov Identifier: NCT04110028
Recruitment Status : Recruiting
First Posted : October 1, 2019
Last Update Posted : November 29, 2019
Sponsor:
Collaborator:
ChromaDex, Inc.
Information provided by (Responsible Party):
Arne Vasli Lund Søraas, Oslo University Hospital

Brief Summary:
Patients will receive oral nicotinamide riboside or placebo and clinical and paraclinical outcome will be determined

Condition or disease Intervention/treatment Phase
Inflammation Acute Illness Drug: Nicotinamide riboside Drug: Placebo Phase 1 Phase 2

Detailed Description:
Patients experiencing acute illness will often have a prolonged recovery time. The cause of this is unknown, but certain factors, like age, duration, and graveness of the illness, is associated with prolonged recovery. In this study, we will investigate whether nicotinamide riboside can shorten the recovery phase and improve outcome after acute illness.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Participants will be randomized to placebo or nicotinamide riboside (NR) in increasing doses. The safety of each dose will be evaluated before commencing the next phase. In each phase nicotinamide or placebo will be administered.

The patients will use NR for 90 days. When all patients have completed their NR treatment the study will be unblinded and the follow-up visits at one year later and further on will be unblinded.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The safety committee will have access to unblinded results during the study.
Primary Purpose: Supportive Care
Official Title: Shorter Recovery Time After Critical Illness
Actual Study Start Date : October 1, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nicotinamide riboside 250 mg
One capsule of 250 mg each morning for three months
Drug: Nicotinamide riboside
Nicotinamide riboside in different doses

Experimental: Nicotinamide riboside 500 mg
One capsule of 250 mg each morning and afternoon for three months
Drug: Nicotinamide riboside
Nicotinamide riboside in different doses

Experimental: Nicotinamide riboside 1000 mg
Two capsules of 250 mg each morning and afternoon for three months
Drug: Nicotinamide riboside
Nicotinamide riboside in different doses

Experimental: Nicotinamide riboside 2000 mg
Four capsules of 250 mg each morning and afternoon for three months
Drug: Nicotinamide riboside
Nicotinamide riboside in different doses

Placebo Comparator: Placebo for 250 mg nicotinamide riboside
One capsule each morning for three months
Drug: Placebo
Placebo

Placebo Comparator: Placebo for 500 mg nicotinamide riboside
One capsule each morning and afternoon for three months
Drug: Placebo
Placebo

Placebo Comparator: Placebo for 1000 mg nicotinamide riboside
Two capsules each morning and afternoon for three months
Drug: Placebo
Placebo

Placebo Comparator: Placebo for 2000 mg nicotinamide riboside
Four capsules each morning and afternoon for three months
Drug: Placebo
Placebo




Primary Outcome Measures :
  1. Length of stay from randomization to discharge from hospital to home or to an institution with a lower care level than a hospital for instance a long term care facility. [ Time Frame: Up to 90 days ]
    Days


Secondary Outcome Measures :
  1. Time to normalization of urine production [ Time Frame: Up to 90 days ]
    Measured in ml/hour

  2. Mortality [ Time Frame: At 90 days, 65 weeks and 10 years ]
    Number of deaths

  3. Length of stay from randomization to medically fit for discharge from hospital to home or to an institution with a lower care level than a hospital for instance a long term care facility. [ Time Frame: Up to 90 days ]
    Days

  4. Time to normalization of blood pressure [ Time Frame: Up to 90 days ]
    Hours/days

  5. Change in blood pressure during the study period [ Time Frame: Baseline and 90 days and 65 weeks ]
    mmHg

  6. Days on respiratory support [ Time Frame: Up to 90 days ]
    Days

  7. Number of days with temperature above 38 at any point from inclusion to discharge. [ Time Frame: Up to 90 days ]
    Days

  8. Number of days with temperature above 38 at any point from inclusion to discharge divided on number of days from inclusion to discharge [ Time Frame: 90 days ]
    Number of days

  9. Duration of stay in ICU after randomization [ Time Frame: Up to 90 days ]
    Days

  10. Number of newly diagnosed infections with identified agent from inclusion to end of trial [ Time Frame: 90 days and 65 weeks ]
    Number

  11. Number of newly diagnosed infections from inclusion to end of trial [ Time Frame: 90 days and 65 weeks ]
    Number

  12. Days on antibiotics from inclusion to end of trial [ Time Frame: 90 days and 65 weeks ]
    Days

  13. Days from inclusion to first antibiotic free day [ Time Frame: Up to 90 days ]
    Days

  14. Highest CRP from inclusion to end of trial [ Time Frame: Up to 90 days ]
    CRP value

  15. Changes in DNA methylation clocks [ Time Frame: At baseline, 90 days and 65 weeks. ]
    Changes in the published DNA methylation clocks by Steve Horvath (Multi tissue, 2013, Skin and Blood, 2018, PhenoAge 2017, GrimAge 2018, telomere length 2019) and Hannum (Hannum clock 2013), Yan Zhang (continous Zhang score, 2017), AgeLab01 (Poster, Gordon Conference, Biology of Aging, July, 2019). All clocks are algorithms based on the Illumina "EPIC" DNA methylation BeadArray.

  16. Changes in DNA methylation measured by the Illumina DNA methylation BeadArray [ Time Frame: At baseline, 90 days and 65 weeks. ]
    Methylation sites (CpG sites) that are differentially changed in the intervention groups compared to the placebo group(s) over the studied time period. Correction for multiple testing will be done.

  17. Change in quality of life [ Time Frame: 14 days prior to admission, baseline, 90 days and 65 weeks ]
    EQ-5D-5L (Quality of life instrument developed by the EuroQol group). Scores ranging from 11111 (full health) to 33333/55555 (worst health).

  18. Change in Katz activities of daily living [ Time Frame: 14 days prior to admission, baseline, 90 days and 65 weeks ]
    Measured at pre-baseline (-14 days), 90 days and 65 weeks. Score 0-6 describing increasing levels of independency.

  19. Change in MoCA [ Time Frame: Day 7, 90 and at 65 weeks ]
    MoCA (Montreal Cognitive Assessment): Score 0-30. Score of 26 or over is considered normal. Lower scores indicates cognitive impairment.

  20. Trail Making Test A [ Time Frame: Day 7, 90 and at 65 weeks ]
    Time in seconds

  21. Trail Making Test B [ Time Frame: Day 7, 90 and at 65 weeks ]
    Time in seconds

  22. Change in forward and backward recall [ Time Frame: Day 7, 90 and at 65 weeks ]
    Test result change over the study period

  23. Change in NEWS score from -4 hours to 0 hours before first tablet to 1,3, 7 days after first capsule [ Time Frame: Four hours before the first administration of NR, at administration of the first capsule and 1, 3 an 7 days after administration of first capsule ]
    NEWS (National Early Warning Score): Score 0-20. High scores indicate high degree of illness.

  24. Change in ECOG status [ Time Frame: 14 days prior to admission, baseline, day 7, day 90 and week 65 ]
    Eastern Cooperative Oncology Group (0-5, higher is worse)

  25. Change in GSC [ Time Frame: Day 1, 3 and 7 ]
    Glasgow Coma Scale

  26. Change in 4 meter walking test [ Time Frame: Baseline, day 7, day 90 and week 65 ]
    Time in seconds

  27. Change in clinical Frailty Score [ Time Frame: Baseline, day 7, day 90 and week 65 ]
    Time in seconds

  28. Change in grip strength over three months [ Time Frame: Baseline, day 7, day 90 and at 65 weeks ]
    Kg measured with a handheld dynamometer

  29. Change in CAM-ICU [ Time Frame: Baseline and day 1,3,7, and every week of hospitalization in ICU ]
    CAM-ICU (Confusion Assessment Method for the ICU): Algorithm of Yes/No questions.

  30. Changes in hearing [ Time Frame: At baseline, 7 and 90 days and 65 weeks ]
    Audiogram

  31. Change in left ventricular ejection fraction [ Time Frame: Baseline, day 7 and at 90 days ]
    Measured with echocardiography

  32. Mitochondrial biogenesis - Respiratory Chain Enzyme Analysis [ Time Frame: Baseline and 90 days ]
    Change from baseline in mitochondrial function at the start and end of the 4 weeks of NR treatment (Respiratory chain enzyme analysis)

  33. Change in mitochondrial biogenesis - mitochondrial DNA quantification [ Time Frame: Baseline to 90 days ]
    Change from baseline in the amount of mitochondrial DNA at the start and end of the 90 days of NR treatment (mtDNA quantification)

  34. Change in NAD+ (nicotinamide adenosine dinucleotide) and related metabolite blood levels [ Time Frame: Baseline, day 7 and day 90 ]
    Blood samples will be analysed using high performance liquid chromatography-mass spectroscopy and kit-based analysis for levels of NAD+ and related metabolites including: nicotinamide-adenine dinucleotide phosphate, nicotinic acid adenine dinucleotide, nicotinamide, and nicotinamide mononucleotide.

  35. Number of readmissions to hospital [ Time Frame: Up to 90 days ]
    Number

  36. Safety - change in blood analytes [ Time Frame: Up to 90 days ]
    Change from baseline in safety blood analyte levels - Sodium potassium phosphate urea creatinine albumin bilirubin carbamide CRP ALP AST ALT LT GT amylase Mg ferritin hemoglobin leucocytes with subgroups thrombocytes Ca INR PH(venous) HCO3(venous) ProBNP HbA1c TSH fT4 folate homocysteine cholesterol LDL HDL CKMB TNT

  37. Safety - adverse events [ Time Frame: Up to 90 days ]
    Adverse events classified according to CTCAE


Other Outcome Measures:
  1. Subgroup analysis - gender [ Time Frame: Ut to 90 days ]
    The primary outcome will be analyzed stratified by gender

  2. Subgroup analysis - age [ Time Frame: Ut to 90 days ]
    The correlation between age and the primary outcome will be measured.

  3. Subgroup analysis - epigenetic age [ Time Frame: Ut to 90 days ]
    The correlation between biological age measured by the DNA methylation based method "GrimAge" (Steve Horvath, 2019 and the primary outcome will be measured.

  4. Subgroup analysis - CRP [ Time Frame: Ut to 90 days ]
    The primary outcome will be analyzed stratified by the maximum measured value of C-reactive protein in plasma of the patient during the hospitalization.

  5. Subgroup analysis - aminoglycosides [ Time Frame: Ut to 90 days ]
    Changes in hearing over the study period will be measured with an audiometer stratified analyses based on the administration of aminoglycosides will be conducted.

  6. Subgroup analysis - NR doses [ Time Frame: Ut to 90 days ]
    The primary outcome will be analyzed stratified by NR dose given to participants.

  7. Subgroup analysis - NR doses [ Time Frame: Baseline, day 7, day 90 and at 65 weeks ]
    Grip strength measured in kg with a handheld dynamometer

  8. Subgroup analysis - NR doses [ Time Frame: Day 7, 90 and at 65 weeks ]
    MoCA will be analyzed stratified by NR dose: MoCA (Montreal Cognitive Assessment): Score 0-30. Score of 26 or over is considered normal. Lower scores indicates cognitive impairment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Adults > 18 years old, admitted to hospital with tissue damage, can be included when they are considered medically stable though still expected to remain hospitalized for at least 7 more days (from inclusion).
  2. Preferably: Previously included in the Janus Cohort or any other cohort or study with stored biological samples.

Exclusion Criteria:

  1. Allergy to NR or ingredients in capsules or placebo.
  2. Patients expected to pass away within 90 days.
  3. Patients unable to give their consent
  4. Unstable patients:

    i. Uncontrolled infection (clinical septicaemia, inadequate response to treatment, inadequate control of source of infection or at treating physician's discretion).

    ii. Mean arterial pressure <70 mm Hg and symptoms of hypotension. iii. Patients requiring dialysis at the time of inclusion or glomerular filtration rate <40 iv. Liver failure with Child-Pugh class B or C or any class associated with hepatic encephalopathy (any grade), alanin aminotransferase or aspartate aminotransferase >3 times upper limit v. Moderate to severe peripheral oedema and/or pulmonary oedema, any unstable cardiac rhythm, myocardial infarction with peak TNT >300 past week. Signs of elevated intracranial pressure (headache, vomiting and depressed global consciousness in conjunction with focal neurological signs, papilledema, spontaneous periorbital bruising and a triad of bradycardia, respiratory depression and hypertension).

    vi. Arterial pH <7.30 or >7.50 vii. Serum potassium under 3,2 or over 5 mmol/L.

  5. Pregnancy or breastfeeding *
  6. Any cancer not in full remission for >10 years
  7. Use of St John's Wort based supplements during the past 30 days
  8. Patient has undergone solid organ transplantation
  9. Participation in any clinical trial with unknown medications
  10. Major gastrointestinal or other internal bleeding past week
  11. Logistical challenges after discharge. Patient must be able to attend follow up.
  12. The treating physician considers the patient unfit or unable to participate. *All fertile women must have a human chorionic gonadotropin test.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04110028


Contacts
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Contact: Arne Søraas, PhD +4790652904 Arne.Vasli.Lund.Soraas@rr-research.no

Locations
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Norway
Oslo University Hospital Recruiting
Oslo, Norway, 0450
Contact: Olaug Reiakvam, MD    91302935 ext 47    olaugm@yahoo.com   
Sponsors and Collaborators
Oslo University Hospital
ChromaDex, Inc.
Investigators
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Principal Investigator: Arne Søraas, PhD Oslo University Hospital
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Responsible Party: Arne Vasli Lund Søraas, Principal Investigator, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT04110028    
Other Study ID Numbers: 2017/1334C
First Posted: October 1, 2019    Key Record Dates
Last Update Posted: November 29, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Sharing of data will be restricted due to European General Data Protection Regulations (GDPR), but the study team will collaborate on analyzing data within these regulations.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Arne Vasli Lund Søraas, Oslo University Hospital:
Nicotinamide riboside
NAD+
Epigenetics
Aging
PARP
Additional relevant MeSH terms:
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Inflammation
Pathologic Processes
Niacinamide
Niacin
Nicotinic Acids
Vitamin B Complex
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents