Nicotinamide Riboside in Hospitalized Patients

Inflammation Clinical Trial

Official title:

Shorter Recovery Time After Critical Illness

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04110028
• Other study ID #: 2017/1334C
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 1, 2019
• Est. completion date: December 1, 2023

Study information

• Verified date: May 2024
• Source: Oslo University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: December 1, 2023
• Est. primary completion date: December 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Illness
• Inflammation

Intervention

Drug:
• Nicotinamide riboside
Nicotinamide riboside in different doses
• Placebo
Placebo

Locations

Country	Name	City	State
Norway	Oslo University Hospital	Oslo

Sponsors (2)

Lead Sponsor	Collaborator
Oslo University Hospital	ChromaDex, Inc.

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Subgroup analysis - gender	The primary outcome will be analyzed stratified by gender	Ut to 90 days
Other	Subgroup analysis - age	The correlation between age and the primary outcome will be measured.	Ut to 90 days
Other	Subgroup analysis - epigenetic age	The correlation between biological age measured by the DNA methylation based method "GrimAge" (Steve Horvath, 2019 and the primary outcome will be measured.	Ut to 90 days
Other	Subgroup analysis - CRP	The primary outcome will be analyzed stratified by the maximum measured value of C-reactive protein in plasma of the patient during the hospitalization.	Ut to 90 days
Other	Subgroup analysis - aminoglycosides	Changes in hearing over the study period will be measured with an audiometer stratified analyses based on the administration of aminoglycosides will be conducted.	Ut to 90 days
Other	Subgroup analysis - NR doses	The primary outcome will be analyzed stratified by NR dose given to participants.	Ut to 90 days
Other	Subgroup analysis - NR doses	Grip strength measured in kg with a handheld dynamometer	Baseline, day 7, day 90 and at 65 weeks
Other	Subgroup analysis - NR doses	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.	Day 7, 90 and at 65 weeks
Primary	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	Up to 90 days
Secondary	Time to normalization of urine production	Measured in ml/hour	Up to 90 days
Secondary	Mortality	Number of deaths	At 90 days, 65 weeks and 10 years
Secondary	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	Up to 90 days
Secondary	Time to normalization of blood pressure	Hours/days	Up to 90 days
Secondary	Change in blood pressure during the study period	mmHg	Baseline and 90 days and 65 weeks
Secondary	Days on respiratory support	Days	Up to 90 days
Secondary	Number of days with temperature above 38 at any point from inclusion to discharge.	Days	Up to 90 days
Secondary	Number of days with temperature above 38 at any point from inclusion to discharge divided on number of days from inclusion to discharge	Number of days	90 days
Secondary	Duration of stay in ICU after randomization	Days	Up to 90 days
Secondary	Number of newly diagnosed infections with identified agent from inclusion to end of trial	Number	90 days and 65 weeks
Secondary	Number of newly diagnosed infections from inclusion to end of trial	Number	90 days and 65 weeks
Secondary	Days on antibiotics from inclusion to end of trial	Days	90 days and 65 weeks
Secondary	Days from inclusion to first antibiotic free day	Days	Up to 90 days
Secondary	Highest CRP from inclusion to end of trial	CRP value	Up to 90 days
Secondary	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.	At baseline, 90 days and 65 weeks.
Secondary	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.	At baseline, 90 days and 65 weeks.
Secondary	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).	14 days prior to admission, baseline, 90 days and 65 weeks
Secondary	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.	14 days prior to admission, baseline, 90 days and 65 weeks
Secondary	Change in MoCA	MoCA (Montreal Cognitive Assessment): Score 0-30. Score of 26 or over is considered normal. Lower scores indicates cognitive impairment.	Day 7, 90 and at 65 weeks
Secondary	Trail Making Test A	Time in seconds	Day 7, 90 and at 65 weeks
Secondary	Trail Making Test B	Time in seconds	Day 7, 90 and at 65 weeks
Secondary	Change in forward and backward recall	Test result change over the study period	Day 7, 90 and at 65 weeks
Secondary	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.	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
Secondary	Change in ECOG status	Eastern Cooperative Oncology Group (0-5, higher is worse)	14 days prior to admission, baseline, day 7, day 90 and week 65
Secondary	Change in GSC	Glasgow Coma Scale	Day 1, 3 and 7
Secondary	Change in 4 meter walking test	Time in seconds	Baseline, day 7, day 90 and week 65
Secondary	Change in clinical Frailty Score	Time in seconds	Baseline, day 7, day 90 and week 65
Secondary	Change in grip strength over three months	Kg measured with a handheld dynamometer	Baseline, day 7, day 90 and at 65 weeks
Secondary	Change in CAM-ICU	CAM-ICU (Confusion Assessment Method for the ICU): Algorithm of Yes/No questions.	Baseline and day 1,3,7, and every week of hospitalization in ICU
Secondary	Changes in hearing	Audiogram	At baseline, 7 and 90 days and 65 weeks
Secondary	Change in left ventricular ejection fraction	Measured with echocardiography	Baseline, day 7 and at 90 days
Secondary	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)	Baseline and 90 days
Secondary	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)	Baseline to 90 days
Secondary	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.	Baseline, day 7 and day 90
Secondary	Number of readmissions to hospital	Number	Up to 90 days
Secondary	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	Up to 90 days
Secondary	Safety - adverse events	Adverse events classified according to CTCAE	Up to 90 days