Clinical trial NCT04110028: Nicotinamide Riboside in Hospitalized Patients
Official title: Shorter Recovery Time After Critical Illness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Inflammation
Acute Illness
Keywords: Nicotinamide riboside
NAD+
Epigenetics
Aging
PARP
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: ChromaDex, Inc.
First posted: 2019-10-01
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: Up to 90 days
Secondary outcomes:
measure: Time to normalization of urine production
timeFrame: Up to 90 days
measure: Mortality
timeFrame: At 90 days, 65 weeks and 10 years
measure: 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.
timeFrame: Up to 90 days
measure: Time to normalization of blood pressure
timeFrame: Up to 90 days
measure: Change in blood pressure during the study period
timeFrame: Baseline and 90 days and 65 weeks
measure: Days on respiratory support
timeFrame: Up to 90 days
measure: Number of days with temperature above 38 at any point from inclusion to discharge.
timeFrame: Up to 90 days
measure: Number of days with temperature above 38 at any point from inclusion to discharge divided on number of days from inclusion to discharge
timeFrame: 90 days
measure: Duration of stay in ICU after randomization
timeFrame: Up to 90 days
measure: Number of newly diagnosed infections with identified agent from inclusion to end of trial
timeFrame: 90 days and 65 weeks
measure: Number of newly diagnosed infections from inclusion to end of trial
timeFrame: 90 days and 65 weeks
measure: Days on antibiotics from inclusion to end of trial
timeFrame: 90 days and 65 weeks
measure: Days from inclusion to first antibiotic free day
timeFrame: Up to 90 days
measure: Highest CRP from inclusion to end of trial
timeFrame: Up to 90 days
measure: Changes in DNA methylation clocks
timeFrame: At baseline, 90 days and 65 weeks.
measure: Changes in DNA methylation measured by the Illumina DNA methylation BeadArray
timeFrame: At baseline, 90 days and 65 weeks.
measure: Change in quality of life
timeFrame: 14 days prior to admission, baseline, 90 days and 65 weeks
measure: Change in Katz activities of daily living
timeFrame: 14 days prior to admission, baseline, 90 days and 65 weeks
measure: Change in MoCA
timeFrame: Day 7, 90 and at 65 weeks
measure: Trail Making Test A
timeFrame: Day 7, 90 and at 65 weeks
measure: Trail Making Test B
timeFrame: Day 7, 90 and at 65 weeks
measure: Change in forward and backward recall
timeFrame: Day 7, 90 and at 65 weeks
measure: Change in NEWS score from -4 hours to 0 hours before first tablet to 1,3, 7 days after first capsule
timeFrame: 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
measure: Change in ECOG status
timeFrame: 14 days prior to admission, baseline, day 7, day 90 and week 65
measure: Change in GSC
timeFrame: Day 1, 3 and 7
measure: Change in 4 meter walking test
timeFrame: Baseline, day 7, day 90 and week 65
measure: Change in clinical Frailty Score
timeFrame: Baseline, day 7, day 90 and week 65
measure: Change in grip strength over three months
timeFrame: Baseline, day 7, day 90 and at 65 weeks
measure: Change in CAM-ICU
timeFrame: Baseline and day 1,3,7, and every week of hospitalization in ICU
measure: Changes in hearing
timeFrame: At baseline, 7 and 90 days and 65 weeks
measure: Change in left ventricular ejection fraction
timeFrame: Baseline, day 7 and at 90 days
measure: Mitochondrial biogenesis - Respiratory Chain Enzyme Analysis
timeFrame: Baseline and 90 days
measure: Change in mitochondrial biogenesis - mitochondrial DNA quantification
timeFrame: Baseline to 90 days
measure: Change in NAD+ (nicotinamide adenosine dinucleotide) and related metabolite blood levels
timeFrame: Baseline, day 7 and day 90
measure: Number of readmissions to hospital
timeFrame: Up to 90 days
measure: Safety - change in blood analytes
timeFrame: Up to 90 days
measure: Safety - adverse events
timeFrame: Up to 90 days
Other outcomes:
measure: Subgroup analysis - gender
timeFrame: Ut to 90 days
measure: Subgroup analysis - age
timeFrame: Ut to 90 days
measure: Subgroup analysis - epigenetic age
timeFrame: Ut to 90 days
measure: Subgroup analysis - CRP
timeFrame: Ut to 90 days
measure: Subgroup analysis - aminoglycosides
timeFrame: Ut to 90 days
measure: Subgroup analysis - NR doses
timeFrame: Ut to 90 days
measure: Subgroup analysis - NR doses
timeFrame: Baseline, day 7, day 90 and at 65 weeks
measure: Subgroup analysis - NR doses
timeFrame: Day 7, 90 and at 65 weeks
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Oslo University Hospital
name: Arne Søraas, PhD
role: PRINCIPAL_INVESTIGATOR
References: