Nicotinamide Riboside in Hospitalized Patients

Oslo University Hospital57 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

QUADRUPLE

Enrollment

Conditions

Inflammation Acute Illness

Interventions

Nicotinamide ribosideDRUG

Nicotinamide riboside in different doses

PlaceboDRUG

Placebo

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (1)

Oslo University Hospital

Oslo, Norway

Outcomes

Primary Outcomes

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.

Days

Time frame: Up to 90 days

Secondary Outcomes

Time to normalization of urine production

Measured in ml/hour

Time frame: Up to 90 days

Mortality

Number of deaths

Time frame: At 90 days, 65 weeks and 10 years

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.

Days

Time frame: Up to 90 days

Time to normalization of blood pressure

Hours/days

Time frame: Up to 90 days

Change in blood pressure during the study period

mmHg

Time frame: Baseline and 90 days and 65 weeks

Days on respiratory support

Days

Time frame: Up to 90 days

Number of days with temperature above 38 at any point from inclusion to discharge.

Days

Time frame: Up to 90 days

Number of days with temperature above 38 at any point from inclusion to discharge divided on number of days from inclusion to discharge

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Duration of stay in ICU after randomization

Days

Time frame: Up to 90 days

Number of newly diagnosed infections with identified agent from inclusion to end of trial

Number

Time frame: 90 days and 65 weeks

Number of newly diagnosed infections from inclusion to end of trial

Number

Time frame: 90 days and 65 weeks

Days on antibiotics from inclusion to end of trial

Days

Time frame: 90 days and 65 weeks

Days from inclusion to first antibiotic free day

Days

Time frame: Up to 90 days

Highest CRP from inclusion to end of trial

CRP value

Time frame: Up to 90 days

Changes in DNA methylation clocks

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.

Time frame: At baseline, 90 days and 65 weeks.

Changes in DNA methylation measured by the Illumina DNA methylation BeadArray

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.

Time frame: At baseline, 90 days and 65 weeks.

Change in quality of life

EQ-5D-5L (Quality of life instrument developed by the EuroQol group). Scores ranging from 11111 (full health) to 33333/55555 (worst health).

Time frame: 14 days prior to admission, baseline, 90 days and 65 weeks

Change in Katz activities of daily living

Measured at pre-baseline (-14 days), 90 days and 65 weeks. Score 0-6 describing increasing levels of independency.

Time frame: 14 days prior to admission, baseline, 90 days and 65 weeks

Change in MoCA

MoCA (Montreal Cognitive Assessment): Score 0-30. Score of 26 or over is considered normal. Lower scores indicates cognitive impairment.

Time frame: Day 7, 90 and at 65 weeks

Trail Making Test A

Time in seconds

Time frame: Day 7, 90 and at 65 weeks

Trail Making Test B

Time in seconds

Time frame: Day 7, 90 and at 65 weeks

Change in forward and backward recall

Test result change over the study period

Time frame: Day 7, 90 and at 65 weeks

Change in NEWS score from -4 hours to 0 hours before first tablet to 1,3, 7 days after first capsule

NEWS (National Early Warning Score): Score 0-20. High scores indicate high degree of illness.

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

Change in ECOG status

Eastern Cooperative Oncology Group (0-5, higher is worse)

Time frame: 14 days prior to admission, baseline, day 7, day 90 and week 65

Change in GSC

Glasgow Coma Scale

Time frame: Day 1, 3 and 7

Change in 4 meter walking test

Time in seconds

Time frame: Baseline, day 7, day 90 and week 65

Change in clinical Frailty Score

Time in seconds

Time frame: Baseline, day 7, day 90 and week 65

Change in grip strength over three months

Kg measured with a handheld dynamometer

Time frame: Baseline, day 7, day 90 and at 65 weeks

Change in CAM-ICU

CAM-ICU (Confusion Assessment Method for the ICU): Algorithm of Yes/No questions.

Time frame: Baseline and day 1,3,7, and every week of hospitalization in ICU

Changes in hearing

Audiogram

Time frame: At baseline, 7 and 90 days and 65 weeks

Change in left ventricular ejection fraction

Measured with echocardiography

Time frame: Baseline, day 7 and at 90 days

Mitochondrial biogenesis - Respiratory Chain Enzyme Analysis

Change from baseline in mitochondrial function at the start and end of the 4 weeks of NR treatment (Respiratory chain enzyme analysis)

Time frame: Baseline and 90 days

Change in mitochondrial biogenesis - mitochondrial DNA quantification

Change from baseline in the amount of mitochondrial DNA at the start and end of the 90 days of NR treatment (mtDNA quantification)

Time frame: Baseline to 90 days

Change in NAD+ (nicotinamide adenosine dinucleotide) and related metabolite blood levels

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.

Time frame: Baseline, day 7 and day 90

Number of readmissions to hospital

Number

Time frame: Up to 90 days

Safety - change in blood analytes

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

Time frame: Up to 90 days

Safety - adverse events

Adverse events classified according to CTCAE

Time frame: Up to 90 days