Nicotinamide Riboside in Hospitalized Patients
- Conditions
- InflammationAcute Illness
- Interventions
- Drug: Placebo
- Registration Number
- NCT04110028
- Lead Sponsor
- Oslo University Hospital
- Brief Summary
Patients will receive oral nicotinamide riboside or placebo and clinical and paraclinical outcome will be determined
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 57
Not provided
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Allergy to NR or ingredients in capsules or placebo.
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Patients expected to pass away within 90 days.
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Patients unable to give their consent
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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.
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Pregnancy or breastfeeding *
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Any cancer not in full remission for >10 years
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Use of St John's Wort based supplements during the past 30 days
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Patient has undergone solid organ transplantation
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Participation in any clinical trial with unknown medications
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Major gastrointestinal or other internal bleeding past week
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Logistical challenges after discharge. Patient must be able to attend follow up.
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The treating physician considers the patient unfit or unable to participate. *All fertile women must have a human chorionic gonadotropin test.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Nicotinamide riboside 500 mg Nicotinamide riboside One capsule of 250 mg each morning and afternoon for three months Placebo for 250 mg nicotinamide riboside Placebo One capsule each morning for three months Placebo for 2000 mg nicotinamide riboside Placebo Four capsules each morning and afternoon for three months Nicotinamide riboside 250 mg Nicotinamide riboside One capsule of 250 mg each morning for three months Placebo for 1000 mg nicotinamide riboside Placebo Two capsules each morning and afternoon for three months Placebo for 500 mg nicotinamide riboside Placebo One capsule each morning and afternoon for three months Nicotinamide riboside 1000 mg Nicotinamide riboside Two capsules of 250 mg each morning and afternoon for three months Nicotinamide riboside 2000 mg Nicotinamide riboside Four capsules of 250 mg each morning and afternoon for three months
- Primary Outcome Measures
Name Time Method 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. Up to 90 days Days
- Secondary Outcome Measures
Name Time Method Time to normalization of urine production Up to 90 days Measured in ml/hour
Days on respiratory support Up to 90 days Days
Days from inclusion to first antibiotic free day Up to 90 days Days
Change in Katz activities of daily living 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.
Change in forward and backward recall Day 7, 90 and at 65 weeks Test result change over the study period
Change in NEWS score from -4 hours to 0 hours before first tablet to 1,3, 7 days after first capsule 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.
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. Up to 90 days Days
Time to normalization of blood pressure Up to 90 days Hours/days
Change in blood pressure during the study period Baseline and 90 days and 65 weeks mmHg
Number of days with temperature above 38 at any point from inclusion to discharge. Up to 90 days Days
Highest CRP from inclusion to end of trial Up to 90 days CRP value
Changes in DNA methylation clocks 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.
Trail Making Test A Day 7, 90 and at 65 weeks Time in seconds
Change in left ventricular ejection fraction Baseline, day 7 and at 90 days Measured with echocardiography
Mortality At 90 days, 65 weeks and 10 years Number of deaths
Number of days with temperature above 38 at any point from inclusion to discharge divided on number of days from inclusion to discharge 90 days Number of days
Number of newly diagnosed infections with identified agent from inclusion to end of trial 90 days and 65 weeks Number
Number of newly diagnosed infections from inclusion to end of trial 90 days and 65 weeks Number
Days on antibiotics from inclusion to end of trial 90 days and 65 weeks Days
Change in MoCA 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.
Changes in DNA methylation measured by the Illumina DNA methylation BeadArray 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.
Change in CAM-ICU 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.
Mitochondrial biogenesis - Respiratory Chain Enzyme Analysis 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)
Number of readmissions to hospital Up to 90 days Number
Duration of stay in ICU after randomization Up to 90 days Days
Change in quality of life 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).
Trail Making Test B Day 7, 90 and at 65 weeks Time in seconds
Change in 4 meter walking test Baseline, day 7, day 90 and week 65 Time in seconds
Change in clinical Frailty Score Baseline, day 7, day 90 and week 65 Time in seconds
Change in grip strength over three months Baseline, day 7, day 90 and at 65 weeks Kg measured with a handheld dynamometer
Safety - adverse events Up to 90 days Adverse events classified according to CTCAE
Changes in hearing At baseline, 7 and 90 days and 65 weeks Audiogram
Change in mitochondrial biogenesis - mitochondrial DNA quantification 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)
Change in NAD+ (nicotinamide adenosine dinucleotide) and related metabolite blood levels 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.
Change in ECOG status 14 days prior to admission, baseline, day 7, day 90 and week 65 Eastern Cooperative Oncology Group (0-5, higher is worse)
Change in GSC Day 1, 3 and 7 Glasgow Coma Scale
Safety - change in blood analytes 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
Trial Locations
- Locations (1)
Oslo University Hospital
🇳🇴Oslo, Norway