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Completed

NCT Number: NCT04110028

Nicotinamide Riboside in Hospitalized Patients

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

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Key information

Conditions

Inflammation Acute Illness Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Oslo University Hospital

Oslo, 0450, Norway

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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).
  • Preferably: Previously included in the Janus Cohort or any other cohort or study with stored biological samples.

Exclusion criteria

  • Allergy to NR or ingredients in capsules or placebo.
  • Patients expected to pass away within 90 days.
  • Patients unable to give their consent
  • 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.

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

Treatment and study plan

Nicotinamide riboside

Drug

Nicotinamide riboside in different doses

Placebo

Drug

Placebo

Primary outcomes

  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 outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Oslo University Hospital

Other

Collaborators

  • ChromaDex, Inc.

Registry information

Official study title

Shorter Recovery Time After Critical Illness

Important dates

Study start
2019
Primary completion
2022
Study completion
2023
First posted
Oct 1, 2019
Registry last updated
May 20, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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