InflammationPhase 1/2NCT04110028
Nicotinamide Riboside in Hospitalized Patients
A Phase 1/2 study testing Nicotinamide riboside in people with Inflammation and Acute Illness, run by Oslo University Hospital at 1 site in Norway.
Trial summary
Patients will receive oral nicotinamide riboside or placebo and clinical and paraclinical outcome will be determined Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Inflammation, Acute Illness
- What is being tested?
- Nicotinamide riboside
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 57 participants
- Where
- 1 siteNorway
- Study dates
- 1 Oct 2019to 1 Dec 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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:
- Uncontrolled infection (clinical septicaemia, inadequate response to treatment, inadequate control of source of infection or at treating physician's discretion).
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Shorter Recovery Time After Critical Illness
Patients will receive oral nicotinamide riboside or placebo and clinical and paraclinical outcome will be determined
Read the 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.
- Conditions
- Inflammation, Acute Illness
- Being tested
- Nicotinamide riboside, Placebo
- Keywords
- Nicotinamide riboside, NAD+, Epigenetics, Aging, PARP
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotinamide ribosideDrug
Nicotinamide riboside in different doses
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Nicotinamide riboside 250 mg | Experimental | One capsule of 250 mg each morning for three months Receives: Drug: Nicotinamide riboside |
| Nicotinamide riboside 500 mg | Experimental | One capsule of 250 mg each morning and afternoon for three months Receives: Drug: Nicotinamide riboside |
| Nicotinamide riboside 1000 mg | Experimental | Two capsules of 250 mg each morning and afternoon for three months Receives: Drug: Nicotinamide riboside |
| Nicotinamide riboside 2000 mg | Experimental | Four capsules of 250 mg each morning and afternoon for three months Receives: Drug: Nicotinamide riboside |
| Placebo for 250 mg nicotinamide riboside | Placebo comparator | One capsule each morning for three months Receives: Drug: Placebo |
| Placebo for 500 mg nicotinamide riboside | Placebo comparator | One capsule each morning and afternoon for three months Receives: Drug: Placebo |
| Placebo for 1000 mg nicotinamide riboside | Placebo comparator | Two capsules each morning and afternoon for three months Receives: Drug: Placebo |
| Placebo for 2000 mg nicotinamide riboside | Placebo comparator | Four capsules each morning and afternoon for three months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 90 days
Secondary outcomes (37)
Time to normalization of urine production
Measured in ml/hour
Measured: Up to 90 days
Mortality
Number of deaths
Measured: 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
Measured: Up to 90 days
Time to normalization of blood pressure
Hours/days
Measured: Up to 90 days
Change in blood pressure during the study period
mmHg
Measured: Baseline and 90 days and 65 weeks
Days on respiratory support
Days
Measured: Up to 90 days
Number of days with temperature above 38 at any point from inclusion to discharge.
Days
Measured: 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
Number of days
Measured: 90 days
Duration of stay in ICU after randomization
Days
Measured: Up to 90 days
Number of newly diagnosed infections with identified agent from inclusion to end of trial
Number
Measured: 90 days and 65 weeks
Number of newly diagnosed infections from inclusion to end of trial
Number
Measured: 90 days and 65 weeks
Days on antibiotics from inclusion to end of trial
Days
Measured: 90 days and 65 weeks
Days from inclusion to first antibiotic free day
Days
Measured: Up to 90 days
Highest CRP from inclusion to end of trial
CRP value
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: Day 7, 90 and at 65 weeks
Trail Making Test A
Time in seconds
Measured: Day 7, 90 and at 65 weeks
Trail Making Test B
Time in seconds
Measured: Day 7, 90 and at 65 weeks
Change in forward and backward recall
Test result change over the study period
Measured: 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.
Measured: 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)
Measured: 14 days prior to admission, baseline, day 7, day 90 and week 65
Change in GSC
Glasgow Coma Scale
Measured: Day 1, 3 and 7
Change in 4 meter walking test
Time in seconds
Measured: Baseline, day 7, day 90 and week 65
Change in clinical Frailty Score
Time in seconds
Measured: Baseline, day 7, day 90 and week 65
Change in grip strength over three months
Kg measured with a handheld dynamometer
Measured: 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.
Measured: Baseline and day 1,3,7, and every week of hospitalization in ICU
Changes in hearing
Audiogram
Measured: At baseline, 7 and 90 days and 65 weeks
Change in left ventricular ejection fraction
Measured with echocardiography
Measured: 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)
Measured: 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)
Measured: 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.
Measured: Baseline, day 7 and day 90
Number of readmissions to hospital
Number
Measured: 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
Measured: Up to 90 days
Safety - adverse events
Adverse events classified according to CTCAE
Measured: Up to 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2019
- Study start1 Oct 2019
- Primary completion1 Dec 2022
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InflammationStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Sequential
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- ChromaDex, Inc.
- Responsible party
- Principal investigator, Arne Vasli Lund Søraas, Oslo University Hospital
- Investigators
- Arne Søraas, PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04110028
- Sponsor's protocol ID
- 2017/1334C
- Status last verified
- May 2024
- First submitted
- 20 Sep 2019
- Last updated
- 20 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Shorter Recovery Time After Critical Illness
- ClinicalTrials.gov ID
- NCT04110028
- Acronym / sponsor ID
- 2017/1334C
- Conditions
- Inflammation, Acute Illness
- Keywords
- Nicotinamide riboside, NAD+, Epigenetics, Aging, PARP
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- ChromaDex, Inc.
- Study start
- 1 Oct 2019 (actual)
- Primary completion
- 1 Dec 2022 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 1 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 8
- 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.
| Arm | Type | Receives |
|---|---|---|
| Nicotinamide riboside 250 mg | Experimental | Drug: Nicotinamide ribosideOne capsule of 250 mg each morning for three months |
| Nicotinamide riboside 500 mg | Experimental | Drug: Nicotinamide ribosideOne capsule of 250 mg each morning and afternoon for three months |
| Nicotinamide riboside 1000 mg | Experimental | Drug: Nicotinamide ribosideTwo capsules of 250 mg each morning and afternoon for three months |
| Nicotinamide riboside 2000 mg | Experimental | Drug: Nicotinamide ribosideFour capsules of 250 mg each morning and afternoon for three months |
| Placebo for 250 mg nicotinamide riboside | Placebo comparator | Drug: PlaceboOne capsule each morning for three months |
| Placebo for 500 mg nicotinamide riboside | Placebo comparator | Drug: PlaceboOne capsule each morning and afternoon for three months |
| Placebo for 1000 mg nicotinamide riboside | Placebo comparator | Drug: PlaceboTwo capsules each morning and afternoon for three months |
| Placebo for 2000 mg nicotinamide riboside | Placebo comparator | Drug: PlaceboFour capsules each morning and afternoon for three months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (15 listed)
- 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:
- Pregnancy or breastfeeding *
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nicotinamide ribosideNicotinamide riboside in different doses | Drug | Nicotinamide riboside 1000 mg, Nicotinamide riboside 2000 mg, Nicotinamide riboside 250 mg, Nicotinamide riboside 500 mg |
| PlaceboPlacebo | Drug | Placebo for 1000 mg nicotinamide riboside, Placebo for 2000 mg nicotinamide riboside, Placebo for 250 mg nicotinamide riboside, Placebo for 500 mg nicotinamide riboside |
Primary outcome
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.
Time frame: Up to 90 days
Days
37 secondary outcomes
Time to normalization of urine production
Time frame: Up to 90 days
Mortality
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.
Time frame: Up to 90 days
Time to normalization of blood pressure
Time frame: Up to 90 days
Change in blood pressure during the study period
Time frame: Baseline and 90 days and 65 weeks
Days on respiratory support
Time frame: Up to 90 days
Number of days with temperature above 38 at any point from inclusion to discharge.
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
Time frame: 90 days
Duration of stay in ICU after randomization
Time frame: Up to 90 days
Number of newly diagnosed infections with identified agent from inclusion to end of trial
Time frame: 90 days and 65 weeks
Number of newly diagnosed infections from inclusion to end of trial
Time frame: 90 days and 65 weeks
Days on antibiotics from inclusion to end of trial
Time frame: 90 days and 65 weeks
Days from inclusion to first antibiotic free day
Time frame: Up to 90 days
Highest CRP from inclusion to end of trial
Time frame: Up to 90 days
Changes in DNA methylation clocks
Time frame: At baseline, 90 days and 65 weeks.
Changes in DNA methylation measured by the Illumina DNA methylation BeadArray
Time frame: At baseline, 90 days and 65 weeks.
Change in quality of life
Time frame: 14 days prior to admission, baseline, 90 days and 65 weeks
Change in Katz activities of daily living
Time frame: 14 days prior to admission, baseline, 90 days and 65 weeks
Change in MoCA
Time frame: Day 7, 90 and at 65 weeks
Trail Making Test A
Time frame: Day 7, 90 and at 65 weeks
Trail Making Test B
Time frame: Day 7, 90 and at 65 weeks
Change in forward and backward recall
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
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
Time frame: 14 days prior to admission, baseline, day 7, day 90 and week 65
Change in GSC
Time frame: Day 1, 3 and 7
Change in 4 meter walking test
Time frame: Baseline, day 7, day 90 and week 65
Change in clinical Frailty Score
Time frame: Baseline, day 7, day 90 and week 65
Change in grip strength over three months
Time frame: Baseline, day 7, day 90 and at 65 weeks
Change in CAM-ICU
Time frame: Baseline and day 1,3,7, and every week of hospitalization in ICU
Changes in hearing
Time frame: At baseline, 7 and 90 days and 65 weeks
Change in left ventricular ejection fraction
Time frame: Baseline, day 7 and at 90 days
Mitochondrial biogenesis - Respiratory Chain Enzyme Analysis
Time frame: Baseline and 90 days
Change in mitochondrial biogenesis - mitochondrial DNA quantification
Time frame: Baseline to 90 days
Change in NAD+ (nicotinamide adenosine dinucleotide) and related metabolite blood levels
Time frame: Baseline, day 7 and day 90
Number of readmissions to hospital
Time frame: Up to 90 days
Safety - change in blood analytes
Time frame: Up to 90 days
Safety - adverse events
Time frame: Up to 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2024.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arne Søraas, PhD principal investigator
Oslo University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Nicotinamide riboside in people with Inflammation and Acute Illness, run by Oslo University Hospital at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: Up to 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2024.