Back to resultsNicotinamide Riboside in Hospitalized Patients
Primary Purpose
Inflammation, Acute Illness
Status
Unknown status
Phase
Phase 1
Locations
Norway
Study Type
Interventional
Intervention
Nicotinamide riboside
Placebo
Sponsored by
About this trial
This is an interventional supportive care trial for Inflammation focused on measuring Nicotinamide riboside, NAD+, Epigenetics, Aging, PARP
Eligibility Criteria
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.
Sites / Locations
- Oslo University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Placebo Comparator
Placebo Comparator
Arm Label
Nicotinamide riboside 250 mg
Nicotinamide riboside 500 mg
Nicotinamide riboside 1000 mg
Nicotinamide riboside 2000 mg
Placebo for 250 mg nicotinamide riboside
Placebo for 500 mg nicotinamide riboside
Placebo for 1000 mg nicotinamide riboside
Placebo for 2000 mg nicotinamide riboside
Arm Description
One capsule of 250 mg each morning for three months
One capsule of 250 mg each morning and afternoon for three months
Two capsules of 250 mg each morning and afternoon for three months
Four capsules of 250 mg each morning and afternoon for three months
One capsule each morning for three months
One capsule each morning and afternoon for three months
Two capsules each morning and afternoon for three months
Four capsules each morning and afternoon for three months
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Time to normalization of urine production
Measured in ml/hour
Mortality
Number of deaths
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 to normalization of blood pressure
Hours/days
Change in blood pressure during the study period
mmHg
Days on respiratory support
Days
Number of days with temperature above 38 at any point from inclusion to discharge.
Days
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
Duration of stay in ICU after randomization
Days
Number of newly diagnosed infections with identified agent from inclusion to end of trial
Number
Number of newly diagnosed infections from inclusion to end of trial
Number
Days on antibiotics from inclusion to end of trial
Days
Days from inclusion to first antibiotic free day
Days
Highest CRP from inclusion to end of trial
CRP value
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.
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.
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).
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.
Change in MoCA
MoCA (Montreal Cognitive Assessment): Score 0-30. Score of 26 or over is considered normal. Lower scores indicates cognitive impairment.
Trail Making Test A
Time in seconds
Trail Making Test B
Time in seconds
Change in forward and backward recall
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
NEWS (National Early Warning Score): Score 0-20. High scores indicate high degree of illness.
Change in ECOG status
Eastern Cooperative Oncology Group (0-5, higher is worse)
Change in GSC
Glasgow Coma Scale
Change in 4 meter walking test
Time in seconds
Change in clinical Frailty Score
Time in seconds
Change in grip strength over three months
Kg measured with a handheld dynamometer
Change in CAM-ICU
CAM-ICU (Confusion Assessment Method for the ICU): Algorithm of Yes/No questions.
Changes in hearing
Audiogram
Change in left ventricular ejection fraction
Measured with echocardiography
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)
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)
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.
Number of readmissions to hospital
Number
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
Safety - adverse events
Adverse events classified according to CTCAE
Full Information
NCT ID
NCT04110028
First Posted
September 20, 2019
Last Updated
March 1, 2021
Sponsor
Oslo University Hospital
Collaborators
ChromaDex, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04110028
Brief Title
Nicotinamide Riboside in Hospitalized Patients
Official Title
Shorter Recovery Time After Critical Illness
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Unknown status
Study Start Date
October 1, 2019 (Actual)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital
Collaborators
ChromaDex, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammation, Acute Illness
Keywords
Nicotinamide riboside, NAD+, Epigenetics, Aging, PARP
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The safety committee will have access to unblinded results during the study.
Allocation
Randomized
Enrollment
84 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Nicotinamide riboside 250 mg
Arm Type
Experimental
Arm Description
One capsule of 250 mg each morning for three months
Arm Title
Nicotinamide riboside 500 mg
Arm Type
Experimental
Arm Description
One capsule of 250 mg each morning and afternoon for three months
Arm Title
Nicotinamide riboside 1000 mg
Arm Type
Experimental
Arm Description
Two capsules of 250 mg each morning and afternoon for three months
Arm Title
Nicotinamide riboside 2000 mg
Arm Type
Experimental
Arm Description
Four capsules of 250 mg each morning and afternoon for three months
Arm Title
Placebo for 250 mg nicotinamide riboside
Arm Type
Placebo Comparator
Arm Description
One capsule each morning for three months
Arm Title
Placebo for 500 mg nicotinamide riboside
Arm Type
Placebo Comparator
Arm Description
One capsule each morning and afternoon for three months
Arm Title
Placebo for 1000 mg nicotinamide riboside
Arm Type
Placebo Comparator
Arm Description
Two capsules each morning and afternoon for three months
Arm Title
Placebo for 2000 mg nicotinamide riboside
Arm Type
Placebo Comparator
Arm Description
Four capsules each morning and afternoon for three months
Intervention Type
Drug
Intervention Name(s)
Nicotinamide riboside
Intervention Description
Nicotinamide riboside in different doses
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
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.
Description
Days
Time Frame
Up to 90 days
Secondary Outcome Measure Information:
Title
Time to normalization of urine production
Description
Measured in ml/hour
Time Frame
Up to 90 days
Title
Mortality
Description
Number of deaths
Time Frame
At 90 days, 65 weeks and 10 years
Title
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.
Description
Days
Time Frame
Up to 90 days
Title
Time to normalization of blood pressure
Description
Hours/days
Time Frame
Up to 90 days
Title
Change in blood pressure during the study period
Description
mmHg
Time Frame
Baseline and 90 days and 65 weeks
Title
Days on respiratory support
Description
Days
Time Frame
Up to 90 days
Title
Number of days with temperature above 38 at any point from inclusion to discharge.
Description
Days
Time Frame
Up to 90 days
Title
Number of days with temperature above 38 at any point from inclusion to discharge divided on number of days from inclusion to discharge
Description
Number of days
Time Frame
90 days
Title
Duration of stay in ICU after randomization
Description
Days
Time Frame
Up to 90 days
Title
Number of newly diagnosed infections with identified agent from inclusion to end of trial
Description
Number
Time Frame
90 days and 65 weeks
Title
Number of newly diagnosed infections from inclusion to end of trial
Description
Number
Time Frame
90 days and 65 weeks
Title
Days on antibiotics from inclusion to end of trial
Description
Days
Time Frame
90 days and 65 weeks
Title
Days from inclusion to first antibiotic free day
Description
Days
Time Frame
Up to 90 days
Title
Highest CRP from inclusion to end of trial
Description
CRP value
Time Frame
Up to 90 days
Title
Changes in DNA methylation clocks
Description
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.
Title
Changes in DNA methylation measured by the Illumina DNA methylation BeadArray
Description
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.
Title
Change in quality of life
Description
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
Title
Change in Katz activities of daily living
Description
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
Title
Change in MoCA
Description
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
Title
Trail Making Test A
Description
Time in seconds
Time Frame
Day 7, 90 and at 65 weeks
Title
Trail Making Test B
Description
Time in seconds
Time Frame
Day 7, 90 and at 65 weeks
Title
Change in forward and backward recall
Description
Test result change over the study period
Time Frame
Day 7, 90 and at 65 weeks
Title
Change in NEWS score from -4 hours to 0 hours before first tablet to 1,3, 7 days after first capsule
Description
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
Title
Change in ECOG status
Description
Eastern Cooperative Oncology Group (0-5, higher is worse)
Time Frame
14 days prior to admission, baseline, day 7, day 90 and week 65
Title
Change in GSC
Description
Glasgow Coma Scale
Time Frame
Day 1, 3 and 7
Title
Change in 4 meter walking test
Description
Time in seconds
Time Frame
Baseline, day 7, day 90 and week 65
Title
Change in clinical Frailty Score
Description
Time in seconds
Time Frame
Baseline, day 7, day 90 and week 65
Title
Change in grip strength over three months
Description
Kg measured with a handheld dynamometer
Time Frame
Baseline, day 7, day 90 and at 65 weeks
Title
Change in CAM-ICU
Description
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
Title
Changes in hearing
Description
Audiogram
Time Frame
At baseline, 7 and 90 days and 65 weeks
Title
Change in left ventricular ejection fraction
Description
Measured with echocardiography
Time Frame
Baseline, day 7 and at 90 days
Title
Mitochondrial biogenesis - Respiratory Chain Enzyme Analysis
Description
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
Title
Change in mitochondrial biogenesis - mitochondrial DNA quantification
Description
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
Title
Change in NAD+ (nicotinamide adenosine dinucleotide) and related metabolite blood levels
Description
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
Title
Number of readmissions to hospital
Description
Number
Time Frame
Up to 90 days
Title
Safety - change in blood analytes
Description
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
Title
Safety - adverse events
Description
Adverse events classified according to CTCAE
Time Frame
Up to 90 days
Other Pre-specified Outcome Measures:
Title
Subgroup analysis - gender
Description
The primary outcome will be analyzed stratified by gender
Time Frame
Ut to 90 days
Title
Subgroup analysis - age
Description
The correlation between age and the primary outcome will be measured.
Time Frame
Ut to 90 days
Title
Subgroup analysis - epigenetic age
Description
The correlation between biological age measured by the DNA methylation based method "GrimAge" (Steve Horvath, 2019 and the primary outcome will be measured.
Time Frame
Ut to 90 days
Title
Subgroup analysis - CRP
Description
The primary outcome will be analyzed stratified by the maximum measured value of C-reactive protein in plasma of the patient during the hospitalization.
Time Frame
Ut to 90 days
Title
Subgroup analysis - aminoglycosides
Description
Changes in hearing over the study period will be measured with an audiometer stratified analyses based on the administration of aminoglycosides will be conducted.
Time Frame
Ut to 90 days
Title
Subgroup analysis - NR doses
Description
The primary outcome will be analyzed stratified by NR dose given to participants.
Time Frame
Ut to 90 days
Title
Subgroup analysis - NR doses
Description
Grip strength measured in kg with a handheld dynamometer
Time Frame
Baseline, day 7, day 90 and at 65 weeks
Title
Subgroup analysis - NR doses
Description
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.
Time Frame
Day 7, 90 and at 65 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Arne Søraas, PhD
Phone
+4790652904
Email
Arne.Vasli.Lund.Soraas@rr-research.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arne Søraas, PhD
Organizational Affiliation
Oslo University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oslo University Hospital
City
Oslo
ZIP/Postal Code
0450
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olaug Reiakvam, MD
Phone
91302935
Ext
47
Email
olaugm@yahoo.com
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Sharing of data will be restricted due to European General Data Protection Regulations (GDPR), but the study team will collaborate on analyzing data within these regulations.
Learn more about this trial
Nicotinamide Riboside in Hospitalized Patients
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