Clinical trial NCT06971224: NADream: Effects of Nicotinamide Adenine Dinucleotide Supplementation on Sleep Quality in Healthy Individuals
Official title: NADream: Effects of Nicotinamide Adenine Dinucleotide Supplementation on Sleep Quality in Healthy Individuals: A Randomized Controlled Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Sleep
Keywords: Sleep
Nicotinamide Riboside
NR
Nicotinamide adenine dinucleotide
NAD
Polysomonography
PSG
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
Collaborators: name: University of Bergen
First posted: 2025-05-14
Enrollment: 16
Sex: ALL
Minimum age (years): 40
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized double-blinded placebo-controlled study with a duration of 8 weeks.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evalue the effects of nicotinamide adenine dinucleotide (NAD) supplementation (nicotinamide riboside (NR) form) on sleep in healthy adults compared to a placebo. NAD is important for brain health and energy balance and a proposed explanation for its effect on sleep is that NAD supplementation restores the neurophysiological capacity of the brain to 'rest' during sleep. If this is the case, we expect the administration to result in improvements in sleep quality (and most likely sleep quantity) compared to placebo. Participants will receive either NAD supplementation or a placebo and their sleep will be measured to detect any differences between the two groups.

Detailed description: Nicotinamide adenine dinucleotide (NAD+) is important for regulating cellular energy metabolism, mitochondrial function, and circadian rhythms, which are key processes involved in the sleep-wake cycle and sleep regulation. Nicotinamide riboside (NR) supplementation has been shown to elevate NAD+ levels in humans. Higher NAD+ levels may support better sleep by restoration of mitochondrial efficiency and reducing oxidative stress.

As people age, there is evidence of a decline in NAD+ levels, which may lead to mitochondrial dysfunction, oxidative stress, and disruptions in circadian rhythms. These changes can negatively affect sleep architecture and reduce sleep quality. Impaired NAD+ metabolism has been linked to problems with the molecular clock, which regulates circadian timing through effects on sirtuin activity and clock genes such as BMAL1. NAD+ also supports brain metabolism by maintaining mitochondrial function, promoting neuroprotection, regulating redox balance, and reducing neuroinflammation. By restoring NAD+ levels, NR supplementation may help improve mitochondrial efficiency, decrease oxidative damage, and enhance sleep-related cellular maintenance. NR may also support synchronization of circadian rhythms, further promoting healthy sleep. Its effects also include modulating neuroinflammatory pathways and strengthening cellular resilience against oxidative stress, both of which are essential for maintaining cognitive functions and neural plasticity during sleep.

The NADream study will test whether NR supplementation can improve both objective and subjective measures of sleep in healthy adults. Sleep will be assessed using polysomnography (PSG), the gold standard for objective sleep measurement, along with actigraphy, Somnofy sleep monitoring, and the Pittsburgh Sleep Quality Index (PSQI). This study will be a randomized, placebo-controlled, double-blind, parallel-group design. Participants will be randomly assigned to receive ether NR or a placebo for 8 weeks. The findings from this study will help determine whether NR supplementation could be a viable therapeutic option to explore further in this area.

Eligibility criteria: Inclusion Criteria:

* Participant must be 40 to 60 years of age inclusive, at the time of signing the informed consent.
* Male or female.
* Participants who are healthy as determined by medical evaluation including medical history and physical examination.
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the study protocol.
* Self-reported normal sleep patterns, assessed by Pittsburgh sleep quality index (PSQI; cutoff ≤ 5).
* No current use of sleep medications or supplements.
* Able to wear polysomnographic equipment and actigraphy during nighttime.

Exclusion Criteria:

* History of sleep disorders (e.g. insomnia, sleep apnea).
* Abnormal findings on PSG, such as sleep related breathing disorders (apnea-hypopnea index (AHI) ≥ 5), sleep related movement disorders (periodic limb movement index (PLMI) ≥ 15, and parasomnias (like REM sleep behavior disorder (RBD)).
* Chronic use of alcohol, tobacco, or medications affecting sleep.
* Significant psychiatric or medical conditions (including neurological, heart, lung, or sleep disorders/diseases).
* Travelled \>1 time zone and night work \<1 month before study, or during the study.
* Extreme chronotype according to the Composite Morningness Questionnaire (evening type; \<22 and morning type \>44).
* Pregnancy.
* Breastfeeding.
* Supplements resulting in \> 20 mg daily of nicotinamide riboside, nicotinamide mononucleotide (NMN), niacin (vitamin B3, nicotinic acid amide or other vitamin B3 analogues) less than 3 months prior to randomization.
* Participation in other clinical trials last 3 months.
* Deemed ineligible by lead principal investigator.

Primary outcomes:
measure: The primary objective is to evaluate the effect of NAD supplementation on objective sleep parameters via polysomnography (PSG).
timeFrame: From enrollment to the end of treatment at 8 weeks.
Secondary outcomes:
measure: The secondary endpoints are to evaluate the effect of NAD supplementation on objective sleep parameters via polysomnography (PSG).
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: EEG power
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: Arousals during sleep.
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: Theta activity.
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: Time in bed (TIB).
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: Sleep onset latency (SOL).
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: Total sleep time (TST).
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: Sleep architecture.
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: Wake after sleep onset (WASO).
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: Sleep efficiency (SE).
timeFrame: From enrollment to the end of treatment at 8 weeks.
Other outcomes:
measure: Cognitive function.
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: Blood biomarkers.
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: NAD metabolome.
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: Blood samples.
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: Subjective sleep parameters using validated questionnaires.
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: Objective activity patterns tracked by non-invasive device.
timeFrame: From enrollment to the end of treatment at 8 weeks.
measure: Objective sleep patterns tracked by non-invasive device.
timeFrame: From enrollment to the end of treatment at 8 weeks.
Locations:
city: Bergen
country: Norway
facility: Haukeland University Hospital
Study officials:
affiliation: Haukeland University Hospital
name: Charalampos Tzoulis, PhD
role: STUDY_DIRECTOR
affiliation: University of Bergen
name: Katarina Lundervold, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Bergen
name: Janne Grønli, PhD
role: PRINCIPAL_INVESTIGATOR
References: