Clinical trial NCT03151707
Conditions: Healthy
Sponsor: Mclean Hospital
Start date: 2017-10-01; Completion date: 2022-09-30
Enrollment: 11 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The primary aim of this study is to investigate the effects of exogenously administered nicotinamide riboside (NR) on brain NAD+/NADH ratio and bioenergetics functions in healthy individuals using phosphorus magnetic resonance spectroscopy (31P MRS) imaging.

The secondary aims are to investigate the change in brain PCr/ATP and creatine kinase enzyme rate after NR use. In addition, NAD+/NADH ratio, PCr/ATP and CK enzyme rate will be measured in the calf muscle, as secondary outcome measures.

Detailed description:

Arms: arm 1: Participants will receive NR at a dose of 2g/day
Interventions: intervention 1: Nicotinamide Riboside
Intervention descriptions: intervention 1: Nicotinamide riboside 2g/day for a 2 week duration

Protocol documents:
Prot_001.pdf: 
PARTNERS HUMAN RESEARCH COMMITTEE 
PROTOCOL SUMMARY 
Partners Human Subjects Research Application Form  
 
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
1 
 
Answer all questions accurately and completely in order to provide the PHRC with the relevant 
information to assess the risk-benefit ratio for the study.  Do not leave sections blank. 
 
PRINCIPAL/OVERALL INVESTIGATOR 
Dost Ongur, MD, PhD Phone: 617-855-3922 
Schizophrenia & Bipolar Disorder Program McLean Hospital, Admissions 
Building, AB 352 115 Mill Street Belmont, MA 02478 e-mail: 
dongur@partners.org 
 
 
PROTOCOL TITLE 
The effects of nicotinamide riboside supplementation on brain NAD+/NADH 
ratio and bioenergetics 
 
 
 
FUNDING 
Department Funds 
 
 
 
VERSION DATE 
12/29/2016 
 
 
 
SPECIFIC AIMS 
Concisely state the objectives of the study and the hypothesis being tested. 
 
The primary aim of this study is to investigate the effects of exogenously 
administered nicotinamide riboside (NR) on brain NAD+/NADH ratio and 
bioenergetics functions in healthy individuals using 31P MRS imaging. 
 
The secondary aim is to investigate the effects of NR on brain structure and 
neurotransmitter functions using other neuroimaging methods. 
 
 
BACKGROUND AND SIGNIFICANCE 
Provide a brief paragraph summarizing prior experience important for understanding the 
proposed study and procedures. 
 


Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
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NAD+ serves broadly two functions: an enzyme cofactor in redox reactions 
and a co-substrate for different classes of enzymes. As a coenzyme, NAD+ is 
essential for energy generation by transferring reducing equivalents from 
glycolysis (from the activity of glyceraldehyde-3-phosphate dehydrogenase) 
and from the TCA cycle under the form of NADH. When oxygen is limiting, 
NADH is converted to NAD+ by reduction of pyruvate into lactate. With 
oxygen, cytoplasmic NADH transfers its reducing equivalent through the 
malateaspartate shuttle or the glycerol-3-3-phosphate shuttle to the 
mitochondrial matrix. These reducing equivalents are oxidized by complex I 
of the electron-transport chain (ETC), thereby coupling glycolysis and the TCA 
cycle to ATP synthesis via oxidative phosphorylation [metabolizma sensoru, 
redox, free radical damage vb. ]. As a co-substrate, NAD+ is consumed by 
three classes of enzymes -(i) the sirtuins (SIRTs), (ii) the adenosine 
diphosphate (ADP) ribose transferases (ARTs) and poly (ADP-ribose) 
polymerases (PARPs), and (iii) the cyclic ADP ribose (cADPR) synthases (CD38 
and CD157)- which are involved in DNA repair, gene expression, regulation of 
energy 
metabolism, 
and 
calcium 
mobilization, 
aging/longevity, 
carcinogenesis, and immunological functions 15, 19.  
    
Despite the crucial roles of NAD+ and NADH (together termed NAD 
metabolites) in cellular metabolism and physiology, their noninvasive in vivo 
detection is extremely challenging. In vivo P MR spectroscopy (MRS) provides 
a critical window into membrane phospholipid metabolism and high-energy 
phosphate molecule dynamics. In addition to commonly observed signals such 
as phosphocreatine (PCr), inorganic phosphate (Pi), and the three adenosine 
triphosphate (ATP) resonances, NAD signals have been identified in 31P 
spectra. However, because of low concentration of NAD metabolites (below 1 
mM), these have previously been considered below the in vivo MRS detection 
limit. Recently, a 31P MRS-based NAD quantification method has been 
developed 
to 
directly 
quantify 
the 
intracellular 
NAD+ 
and 
NADH 
concentrations in vivo and we implemented this method at our 4T scanner.   
 
Several pathways that NAD+ and NADH involved are also implicated in the 
pathophysiology of mood disorders and schizophrenia, including mitochondrial 
dysfunction 1-3, impaired bioenergetics 4, neuro-inflammation 5-8, and 
oxidative stress 9-12. We investigated the brain NAD+ and NADH levels in SZ 
patients with chronic, well-established illness as well as first-episode SZ 
patients who have not been exposed to the confounding effects of chronic 
medication treatment and chronic psychosis. We also included a first-episode 
bipolar disorder (BD) cohort, as a psychiatric control group. Our results 
showed a significant reduction in the NAD+/NADH ratio (Rx) both in 
chronically ill SZ and in first-episode SZ patients. These findings provide 
evidence for redox imbalance in the brain in all phases of SZ, potentially 
reflecting oxidative stress. 
 


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NAD+ is consumed by the enzymes and continuously degraded. To generate 
NAD+, organisms can use de novo synthesis from tryptophan but mainly 
depend on salvage pathways that involves synthesis from vitamin B3 
derivatives nicotinic acid, nicotinamide, and nicotinamide riboside (NR). NR is 
the most recently discovered salvageable NAD+ precursor and is found in 
nutrients such as cow milk and yeast containing food products, however, in 
low quantities. In yeast, assimilation of endogenous NR has been shown to be 
essential for calorie restriction-mediated life-span extension [14] and 
exogenously added NR doubles intracellular NAD+ in a nicotinic acid depleted 
medium, leading to doubling of replicative longevity [7]. 
NR is also a potent stimulator of NAD+ production in several cultured 
mammalian cell types, including mouse and human cells. Increases in NAD+ 
were in some cases as high as 270% of controls [4], levels unprecedented for 
nicotinamide or nicotinic acid as NAD+ sources. 
Several recent studies, including in vivo studies in rodents and in human cell 
cultures demonstrated robust beneficial effects of exogenously administered 
NR on mitochondrial functions, peripheral and CNS metabolism, DNA damage 
and inflammatory activity : 
 
[1] In pre-diabetic mice, NR improved glucose tolerance, reduced weight gain, 
liver damage and the development of hepatic steatosis while protecting 
against sensory neuropathy. In type 2 diabetes model mice, NR greatly 
reduced non-fasting and fasting blood glucose, weight gain and hepatic 
steatosis while protecting against diabetic neuropathy. 
 
[2] NR increased NAD+ levels in muscle and liver, in mice.  Animals challenged 
with high-fat diet were protected from body weight gain, and had enhanced 
endurance and improved oxidation of fatty acids as a fuel source. NR also 
markedly improved insulin sensitivity. NR treatment increased mitochondrial 
biogenesis as measured by higher cristae content in muscle tissue. Consistent 
with increases in tissue NAD+ levels, sirtuins SIRT1 and SIRT3 appeared to 
be upregulated, as measured by FOXO1 and SOD2 acetylation levels. In these 
studies, NR was also shown to have a greater ability to increase NAD+ level 
than other NAD+ precursors such as NMN, nicotinamide, and nicotinic acid. 
Nicotinamide riboside increases NAD+/NADH, which could contribute to its 
ability to enhance mitochondrial oxidative capacity. 
 
[3] High-fat high-sucrose diet was used to elicit chronic hepatosteatosis in 
mice resembling human fatty liver. This also lead to lowered hepatic NAD+ 
levels driving reductions in hepatic mitochondrial content, function, and 
adenosine triphosphate (ATP) levels. NR added to this diet prevented and 
reverted non-alcoholic fatty liver disease by inducing a SIRT1- and SIRT3-
dependent mitochondrial unfolded protein response, triggering an adaptive 
mitohormetic pathway to increase hepatic b-oxidation and mitochondrial 
complex content and activity. 
 


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Version Date:  October 15, 2014 
 
  
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[4] NR supplementation increases total NAD+ in primary  cortical  astrocytes 
obtained from non-transgenic and mutant human superoxide dismutase 
(hSOD1) overexpressing mice. Because total NAD+ increases more than total 
NADH levels (about 100 and 35% change, respectively), treatments also 
modify the NAD+/NADH ratio. Mitochondrial NAD+ is also increased, but no 
significant change was observed in mitochondrial NADH. In the same study, 
NMN treatment confers astrocyte resistance to oxidative stress as reflected by 
reduced vulnerability to H2O2 treatment. Likewise, overexpression of NAMPT 
or mNAMPT also provides protection and reduces mitochondrial ROS 
production 
in 
response 
to 
H2O2. 
Moreover, 
NMN 
treatment 
and 
overexpression of NAMPT or mNAMPT also appear to decrease mitochondrial 
ROS levels under basal conditions. 
 
[5] Treatment with NR treatment increased NAD+ concentration in muscle 
stem cells (MuSCs) and the number of MuSCs in young and old  mice. In old 
mice only, NR treatment reduced nuclear DNA damage, pro-inflammatory 
proteins, increased TCA cycle genes, oxidative phosphorylation, mitochondrial 
membrane potential and increased abundance of ATP in MuSCs. In further 
experiments, NR also increased the number of neural and melanocyte stem 
cells, and slightly increased mouse lifespan.  
   
[6] NR treatment of cultured fibroblasts increased mitochondrial membrane 
potential 
and 
DNA 
content, 
however, 
did 
not 
affect 
expression 
  levels 
  of 
  nDNA- 
  or 
  mtDNA-encoded 
respiratory   complex   subunits. 
     
[7] 
Increasing 
cochlear 
NAD+ 
levels 
by 
NR 
prevents 
noise-
induced   hearing   loss and spiral ganglia neurite degeneration. These effects 
are mediated by the NAD+-dependent mitochondrial sirtuin, SIRT3. 
 
[8] NR given to a mouse model of mitochondrial myopathy increased 
cytochrome c oxidase activity, amount of oxidative phosphorylation enzymes 
and the number of mitochondria in skeletal muscle. Similarly, in brown 
adipose tissue, NR increased mitochondrial number and size, and mtDNA 
amount.  
 
Despite the consistent evidence indicating that NR increases NAD+/NADH 
ratio in several tissues with concomitant effects summarized above, no study 
to date has investigated the in vivo effects of NR in human CNS. In this study, 
we propose to administer NR to healthy human subjects and measure the 
NAD/NADH ratio and bioenergetic functions in the brain using 31P MRS. We 
hypothesize that NR treatment will increase the NAD/NADH ratio in the healthy 
human subjects and improve energy metabolism.    
 


Partners Human Subjects Research Application Form 
  
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Version Date:  October 15, 2014 
 
  
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RESEARCH DESIGN AND METHODS 
Briefly describe study design and anticipated enrollment, i.e., number of subjects to be enrolled 
by researchers study-wide and by Partners researchers.  Provide a brief summary of the 
eligibility criteria (for example, age range, gender, medical condition).  Include any local site 
restrictions, for example, “Enrollment at Partners will be limited to adults although the sponsor’s 
protocol is open to both children and adults.”
We plan to study the levels of chemicals associated with cellular energy 
metabolism; kinetics of enzymes involved in cellular energy metabolisms in 
brains of healthy people before and after use of nicotinamide riboside (NR) for 
2 weeks. In addition, we will also collect data on the structure of the gray 
matter and white matter; resting state functional brain activity; levels of brain 
chemicals including glutamate and GABA; and white matter integrity. We will 
collect whole brain data where possible and focus on the medial prefrontal 
cortex and parietal cortex as two regions of interest where whole-brain data 
collection is not possible due to technical limitations. Data collection for each 
of these modalities is identical to our ongoing patient MRI studies which are 
all IRB approved. We hypothesize that bioenergetics parameters will change 
after the use of NR. Investigation of these parameters in healthy people will 
give us a chance to determine the alterations related to drug itself, 
independent from the pathophysiology of the illness. 
 
Enrolment: The study will enroll up to 60 healthy people with no individual 
history of psychiatric illness and family history of psychotic and mood 
disorders. Family history will be obtained via self-report only. Participants will 
be recruited via online advertisements and flyers as well as approaching 
healthy individuals who previously participated in our studies. Flyers will be 
distributed throughout the hospital. All advertisements and flyers will be 
approved by the PHRC. 
 
Participants will be pre-screened with an IRB-approved telephone interview 
(attached) prior to coming to the Brain Imaging Center. An investigator 
associated with the program approaches participants with information about 
the study. If the participant is interested, he/she will be invited to hospital for 
study visit. During the study visit the investigator (Dr. Chouinard; Dr. Baker; 
Dr. Shinn; Dr. Murphy; one of them will be present in each steps of the study 
according to their availability) will give information about the study again and 
conduct the consent process. 
 
There are no restrictions on subject recruitment based on sex, ethnic 
background or health status other than those mentioned below. Individuals 
who do not speak English will not be allowed to participate in this study. 
 
Inclusion Criteria 
1. 
Age: 18-65 year-old  
2. 
Male or female 


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3. 
Without psychiatric diagnosis according to a structured psychiatric 
interview (SCID; First et al 1994) 
4. 
Without history of a psychotic disorder and/or mood disorder among 
parents, siblings, or children, as obtained via self-report only.  
 
Exclusion Criteria 
1. 
Significant medical or neurological illness. 
2. 
Diagnosis diabetes mellitus (DM), uncontrolled hypertension (HTN), 
severe hypotension, coronary artery disease (CAD), metabolic syndrome, 
glaucoma, liver impairment, decreased renal function, respiratory disorders, 
uncontrolled peptic ulcer disease. 
3. 
Taking any other medications, including over the counter supplements 
with the exception of oral contraceptives for women 
4. 
Pregnancy. Females of child-bearing age must be using an effective 
contraceptive method. 
5. 
History of smoking, substance abuse or dependence. 
6. 
Contraindication to MR scan (claustrophobia, cardiac pacemakers, 
metal clips and stents on blood vessels, artificial heart valves, artificial arms, 
hands, legs, etc., brain stimulator devices, implanted drug pumps, ear 
implants, eye implants or known metal fragments in eyes, exposure to 
shrapnel or metal filings, other metallic surgical hardware in vital areas, 
certain tattoos with metallic ink, certain transdermal patches, metal- 
containing IUDs) 
7. 
Medical condition that would prevent blood draws, including current 
anti-coagulant or anti-aggregant therapy, tendency for abnormal scarring 
(e.g. keloids). 
8. 
Difficulty in swallowing capsules. 
 
 
 
Briefly describe study procedures.  Include any local site restrictions, for example, “Subjects 
enrolled at Partners will not participate in the pharmacokinetic portion of the study.”  Describe 
study endpoints.
 
This study will be comprised of three main parts. All participants will be asked 
not to use alcohol or any other substances and drugs during study period. 
1. The First Part of the Study 
The first part of the study will be carried out within 10 days of study 
entrance and consists of 3 separate visits which will take about 6 hours in 
total. This part of the study will consist of the following procedures: 
A. 
Consenting procedures (20 minutes) 
B.     Clinical evaluation (60 minutes) 
i. 
Structured Clinical Interview for DSM-IV (SCID; (First et al., 1997)) to 
establish absence of Axis I psychiatric diagnoses 
ii. 
Montgomery-Asberg Depression Rating Scale (MADRS) 


Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
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iii. 
Young Mania Rating Scale (YMRS) 
iv. 
Beck Anxiety Inventory (BAI) 
v. 
MOCA (Montreal Cognitive Assessments) 
vi. 
Pittsburgh Sleep Quality Index 
vii. 
Sleep Log 
viii. 
Edinburgh Handedness Survey 
ix. 
North American Adult Reading Test (NAART) 
x. 
DIGS Ethnicity Cards (including Parents and Grandparents) 
xi. 
Medical Questionnaire 
xii. 
Baecke Questionnaire of Habitual Physical Activity 
  
C. Urine toxicology screen (5 minutes) and urine pregnancy test (5 minutes) 
prior to each MRI procedure 
D. MRI procedure: 
i. 
Diagnostic MRI scan at 3T (15 minutes) 
ii. 
Common Anatomic Protocol (CAP) at 3T (MR Scan at 3T-1): Structural 
MRI, resting functional MRI and DTI + long MPRAGE at 3T (28 minutes) 
iii. 
MRS protocol to quantify Glu and GABA at 3T (MR Scan at 3T- 
2) 
(30 minutes) 
iv. 
Phosphorous MRS/MT at 4T (MR Scan at 4T- 1) (90 minutes) 
v. 
Diffusion Tensor Spectroscopy (DTS) at 4T (MR Scan at 4T- 2) 
(90minutes) 
E. Blood draw of 30 ml (10 minutes) 
i. 
HCG, CBC, LFT, BUN, U&E, Lipid Panel, HgA1c, Insulin, Prolactin 
F. Assessment of vital signs (blood pressure, heart rate, temperature), 
weight, height, waist and hip circumference (5 minutes) 
G. EKG (10 minutes) 
H. Filling out a food diary form (All participants will be asked to fill out a food 
diary form for the last 4 days before starting their medication process) 
 
Participants will go into the medication process after completion of all 
procedures in this part of the study. Some participants may be excluded based 
on their psychiatric and medical conditions and laboratory tests at the end of 
the initial investigations. 
 
 
2. The Second Part of the Study 
The second part of the study in which participants will take daily NR will be 
carried out within the next 3 weeks. There will be 4 separate visits during 
this period on the 1st, 2nd, 5th and 9th days.    
 
Participants will take daily 1000 mg NR orally, in the morning, for 16 
consecutive days. NIAGEN®, the commercially available form of nicotinamide 
riboside, will be used as medication. The medication will always begin on 


Partners Human Subjects Research Application Form 
  
Filename: Protocol Summary 
Version Date:  October 15, 2014 
 
  
8 
weekdays except Friday. On the 1st and 2nd day of the medication, 
participants will be asked to take their drugs at McLean Hospital as some side 
effects may occur more often at the beginning of the medication. Observation 
of medication intake will only take place on these days. After they take their 
drugs we will monitor them closely for 1 hour to observe any side effects. The 
participant will then be able to leave the hospital, in case of absence of any 
side effects at the end of the monitoring period. If the participants do not have 
any unacceptable side effects in the first two days, then they will be able to 
take the remaining doses at home. We will provide them sufficient number of 
drugs to take at home. In case of unacceptable side effects, participation will 
be terminated.  
 
Additional visits will be on the 5th and 9th days. These visits will not include 
observation of drug intake but will include assessment of weight, vital signs 
(blood pressure, heart rate, temperature), blood glucose and will take about 
30 minutes. In addition, a blood draw will be carried out on the 5th day to 
measure CBC, LFT, BUN, U&E. These follow-up visits will take place in an 
interview room at the Admissions Building 3rd floor where our research offices 
are located. During these follow up visits, the participant will be interviewed 
by a physician (Dr. Chouinard; Dr. Baker; Dr. Shinn; Dr. Murphy; one of them 
will be present in each steps of the study according to their availability) to 
assess for any developing adverse effects from the medication. If there is any 
concern for treatment- emergent adverse effects, drug administration will be 
discontinued. 
 
Participants will also be asked to fill out a food diary for the last 4 days of their 
medication period (between 13-16 days). 
 
Taking medication regularly is very important for the reliability of this study. 
However, we recognize that some participants may skip taking their drugs in 
some days. We will still complete the study with participants who miss up to 
3 days of medication administration except any one of the last 3 days, and 
qualify those participants as having received the intended course of 
medication (while recording their degree of noncompliance). Participants who 
miss more than 3 days of medication or on any of the days within the last 3 
days will be discontinued from the study.  
 
3. 
The Third Part of the Study 
As we want to investigate the effects of NR on brain structure all participants 
will undergo final investigations on the last two days of the medication 
protocol. These two days will not include observation of drug intake. We will 
split the MR procedure into two days. Participants will undergo 4T MR scan on 
one scan day and all other assessment and 3T MR scans will be done on 
another day. Days will be determined depending on the availability of the 
scanners. In addition, there will be clinical evaluation, assessment of vital 


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9 
signs and blood draw on the first day of the third part of the study (15th day 
of medication intake).  
 
Third part of the study will consist of the following procedures: 
a. 
Clinical evaluation (30 minutes) 
i. 
Montgomery-Asberg Depression Rating Scale (MADRS) 
ii. 
Young Mania Rating Scale (YMRS) 
iii. 
Beck Anxiety Inventory (BAI) 
iv. 
MOCA (Montreal Cognitive Assessments) 
v. 
Pittsburgh Sleep Quality Index 
vi. 
Sleep Log 
 
b. 
Urine toxicology screen (5 minutes) and urine pregnancy test (5 
minutes) prior to each MRI procedure 
c. 
MRI procedure: 
i. 
Common Anatomic Protocol (CAP) at 3T (MR Scan at 3T- 1): Structural 
MRI, resting functional MRI and DTI + long MPRAGE at 3T (28 minutes) 
ii. 
MRS protocol to quantify Glu and GABA at 3T (MR Scan at 3T-2) (30 
minutes) 
iii. 
Phosphorous MRS/MT at 4T (MR Scan at 4T- 1) (90 minutes) 
iv. 
Diffusion Tensor Spectroscopy (DTS) at 4T (MR Scan at 4T- 2) 
(90minutes) 
d. 
Blood draw of 30 ml to study CBC, LFT, BUN, U&E, Lipid Panel, HgA1c, 
Insulin, Prolactin (10 minutes) 
e. 
Assessment of vital signs (blood pressure, heart rate, temperature), 
weight, height, waist and hip circumference (5 minutes) 
 
 
THE FIRST PART OF THE STUDY 
VISIT 1 (at McLean 
Hospital) 
1. 
Consenting procedure 
2. 
Clinical evaluation 
3. 
Urine toxicology screen and urine pregnancy test  
4. 
Blood drawn (HCG, CBC, LFT, BUN, U&E, Lipid Panel, HgAlc, 
Insulin, Prolactin) 
5. 
Assessment of vital signs (blood pressure, heart rate, temperature), 
weight, height, waist, hip circumference 
6. 
EKG 
7. 
Diagnostic MR Scan at 3T 
 
VISIT 2 (at McLean 
Hospital) 
1.                Urine toxicology screen and urine pregnancy test  
2.               MR Scan at 4T- 1 (Phosphorous MRS/MT) 
 


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Version Date:  October 15, 2014 
 
  
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VISIT 3 (at McLean 
Hospital) 
1. 
Urine toxicology screen and urine pregnancy test 
2. 
MR Scan at 3T- 1 (Common Anatomic Protocol) 
3. 
MR Scan at 3T- 2 (MRS protocol to quantify Glu and GABA) 
4. 
MR Scan at 4T- 2 (Diffusion Tensor Spectroscopy) 
 
Filling out a food diary for 4 days 
THE SECOND PART OF THE STUDY 
 
DAY 1  
VISIT 1 (at McLean 
Hospital) 
1. 
NR 1000 mg/d, PO 
2. 
Observation for 1 hour 
3. 
Assessment of vital signs  
4. 
Blood glucose test 
 
 
DAY 2  
VISIT 2 (at McLean 
Hospital) 
1. 
NR 1000 mg/d, PO  
2. 
Observation for 1 hour 
3. 
Assessment of vital signs  
4. 
Blood glucose test 
 
 
DAY 3-4 (at home) 1. 
NR 1000 mg/d, PO 
 
 
DAY 5  
VISIT 3 (at McLean 
Hospital) 
1. 
NR 1000 mg/d, PO  
2. 
Assessment of vital signs  
3. 
Weight measurement 
4. 
Blood glucose test 
5. 
Blood drawn (CBC, LFT, BUN, U&E) 
 
 
 
DAY 6-8 (at home) 1. 
NR 1000 mg/d, PO  
 
 
DAY 9  
VISIT 4 (at McLean 
Hospital) 
1. 
NR 1000 mg/d, PO  
2. 
Assessment of vital signs  
3. 
Weight measurement 
4. 
Blood glucose test 
 
 
Filling out a food 
diary between 13th -
16h days 
DAY 10-14 (at 
home) 
1. 
NR 1000 mg/d, PO  
 
 


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Version Date:  October 15, 2014 
 
  
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THE THIRD PART OF THE STUDY 
DAY 15  
VISIT 1 (at McLean 
Hospital) 
1. 
NR 1000 mg/d, PO  
2. 
Clinical evaluation 
3. 
Blood drawn (CBC, LFT, BUN, U&E, Lipid Panel, HgAlc, Insulin) 
4. 
Urine toxicology screen and urine pregnancy test  
5. 
Assessment of vital signs, weight, waist, hip circumference 
6. 
MR Scan at 3T- 1 (Common Anatomic Protocol) 
7. 
MR Scan at 3T- 2 (MRS protocol to quantify Glu and GABA) 
 
DAY 16  
VISIT 2 (at McLean 
Hospital) 
1. 
Urine toxicology screen and urine pregnancy test 
2. 
MR Scan at 4T- 1 (Phosphorous MRS/MT) 
3. 
MR Scan at 4T- 2 (Diffusion Tensor Spectroscopy) 
 
 
 
 
 
For studies involving treatment or diagnosis, provide information about standard of care at 
Partners (e.g., BWH, MGH) and indicate how the study procedures differ from standard care.  
Provide information on available alternative treatments, procedures, or methods of diagnosis.
 
N/A 
 
 
Describe how risks to subjects are minimized, for example, by using procedures which are 
consistent with sound research design and which do not unnecessarily expose subjects to risk or 
by using procedures already being performed on the subject for diagnostic or treatment purposes.
Participants will be monitored very closely by research stuff members 
including a physician (Dr. Chouinard ; Dr. Baker; Dr. Shinn; Dr. Murphy; one 
of them will be present in each steps of the study according to their 
availability) throughout the whole study. The presence of a qualified physician 
in all steps of the study will maintain the level of observation and guard against 
development of negative sequelae. The physician will be responsible for the 
safety of the subjects and interfere to prevent or reduce any unacceptable 
side effects. If the participants experience a poor reaction to any portion of 
the study, they are invited to take a break, or to withdraw completely. If they 
insist on continuing, but they are affected adversely, the research staff 
member will stop the study intervention at their discretion. 
 


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Medication: There are no published long-term studies of NR in humans which 
document its pharmacokinetic properties. However, we decided to give 
medication for 2 weeks because longer durations decrease compliance and 
shorter durations may lead to a failure to reach steady state concentrations in 
the brain and/or brain changes.  
 
We determined the dose as 1000 mg/day. In a recent study in humans, single 
dose of 1000 mg/day NR did not induce any side effects despite significant 
increases in NAD+ and related metabolites. Moreover, 14-day use in rats at 
doses as high as 5g/kg/day only lead to minor weight reduction and no gross 
pathological changes.  
 
To protect the participants from potential side effects or toxicities, only the 
participants who do not have a past or current medical condition will be 
recruited in this study. At the beginning of the study we will learn about 
participants’ medical conditions and possible risk factors, via clinical 
evaluation, family histories, blood tests (CBC, LFT, BUN, U&E, Lipit Panel, 
HgA1c, Insulin, prolactin), EKG, assessment of weight, height, waist 
circumference, blood pressure and BMI. Participants who have any psychiatric 
or medical conditions will be excluded. Participants who do not have a 
diagnosis of any metabolic disease before but have increased levels of glucose, 
lipid, insulin, HgA1C and prolactin in their laboratory tests and alterations in 
their EKG results will also be excluded at the beginning of the study. When we 
identify these subjects, we will contact their primary care physician 
immediately; and in extreme cases, we may refer the patient to the 
emergency department for immediate evaluation. For subjects without a 
primary care physician, but not requiring emergency attention, we will refer 
the patient to a medical clinic. 
 
To assess very closely the potential side effects of NR, we set up 5 separate 
visits on the 1st, 2nd, 5th, 9th, 14th days of medication period. A physician 
(Dr. Chouinard ; Dr. Baker; Dr. Shinn; Dr. Murphy; one of them will be present 
in each steps of the study according to their availability) will be present to 
monitor all participants’ reactions to the medication and stop the study if they 
are affected adversely. 
 
MRI/MRS Scan: With respect to the magnetic resonance scanner, we have 
found that most subjects find that remaining in the scanner is somewhat 
uncomfortable but acceptable. An MRI technologist will be able to 
communicate with subjects at all times via intercom. Subjects are informed 
that they are free to stop at any point. Approximately 4% of total studies are 
terminated early due to discomfort. Padding around the head will protect 
subjects from minor mechanical injuries and reduce head motion. Earplugs 
will be used to minimize the scanning noise of MR scanner. 
Subjects are thoroughly screened for MR contraindications both by the 
research assistant and the MR technologists or authorized personnel, who 


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must ultimately authorize that it is safe for the subject to go into the scanner. 
A metal-detecting wand is used to identify any metal in or on the patient of 
which the patient may be unaware. If any subjects have had a surgical 
implant, they will not be scanned without proper medical documentation. 
During the MRI or MRS scans and stimulation paradigms participants are free 
to stop the experiment any time by communicating the personnel and the 
experiment will be stopped by the personnel if any adversity is observed. A 
qualified physician (Dr. Chouinard; Dr. Baker; Dr. Shinn; Dr. Murphy; one of 
them will be present in each steps of the study according to their availability) 
will be present in all phases of the screening process. 
 
Women of childbearing age: The effects of nicotinamide riboside on the 
developing fetus and the pregnant women are not known.  While there are 
also no known risks for fetuses, the safety of MRI for pregnant women, women 
of childbearing potential, and nursing mothers has not been established. 
Pregnant women and nursing mothers cannot participate to this study. If the 
participant is a woman of childbearing potential, she must be using a metal-
free IUD, oral contraceptive, barrier methods or must be abstinent (for at least 
1 month: time to get the most reliable result with pregnancy test) prior to this 
study. All women of childbearing age must have a negative blood pregnancy 
test (instead of urine pregnancy test) at the beginning of the study and urine 
pregnancy tests prior to MRI procedures. They must go on using the same 
method of contraception or stay abstinent (if she does not use contraception) 
during the study. 
 
Blood Draw: Subjects will be monitored for 15 minutes following the blood 
draw to ensure they are doing well. To minimize the possibility of bruising and 
infection from the blood proper sterile phlebotomy techniques will be used 
 
Psychiatric Evaluation: Some subjects might feel uncomfortable answering 
questions during the psychiatric evaluation. They will not be forced to answer 
if they do not wish to answer any particular question. If suicidality is expressed 
during the psychiatric interview or in response to study instruments, one of 
the licensed clinicians involved in the study (Dr. Shinn, Dr, Chouinard, Dr. 
Baker, Dr. Murphy) will immediately evaluate and refer the patient for 
appropriate care. In extreme cases, patient will be referred to the emergency 
department for immediate evaluation.      
 
Describe explicitly the methods for ensuring the safety of subjects.  Provide objective criteria for 
removing a subject from the study, for example, objective criteria for worsening disease/lack of 
improvement and/or unacceptable adverse events.  The inclusion of objective drop criteria is 
especially important in studies designed with placebo control groups.
Participants who have any psychiatric or medical conditions will not be 
included in this study. 
 


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Participants who do not have a diagnosis of any metabolic disease before but 
have increased levels of glucose, lipid, insulin, HgA1C and prolactin in their 
laboratory tests and alterations in their EKG results will also be excluded at 
the beginning of the study. 
 
Women of childbearing age who are not using a contraceptive method or not 
staying abstinent (if not using contraceptive methods) or have a positive 
pregnancy test at any point will not be included. 
 
In case of determining any of these conditions in control visits during 
medication period, NR administration will be stopped immediately and the 
study will be terminated for that participant: 
• 
Abnormal vital signs: Heart rate > 100/minute or < 60/minute, or 
systolic blood pressure > 160 mmHg or < 100 mmHg, or body temperature > 
37.5 oC 
• 
CBC, Chem-7 panel, LFT, U&E, BUN values outside of normal range.   
• 
EKG abnormalities 
 
 
 
 
FORESEEABLE RISKS AND DISCOMFORTS 
Provide a brief description of any foreseeable risks and discomforts to subjects.  Include those 
related to drugs/devices/procedures being studied and/or administered/performed solely for 
research purposes.  In addition, include psychosocial risks, and risks related to privacy and 
confidentiality.  When applicable, describe risks to a developing fetus or nursing infant.
 
Medication:  There are no known side effects of NR in humans. A recent study 
investigated the genotoxicity and toxicology of NR to determine the lowest 
observed adverse effect level (LOAEL)) and the maximum level of intake at 
which no adverse health effects are observed (the no observed adverse effect 
level (NOAEL)), and derive the tolerable upper intake level (UL) which is the 
threshold above which the risk of adverse effects increase. This study found 
no genotoxicity at any of the doses applied for the in vitro tests or up to 2g/kg 
in the in vivo experiment in rats. Single dose at 5g/kg lead to no mortalities, 
clinical signs, or gross pathological lesions. In 14-days toxicology studies, a 
minimal reduction in mean body weight was observed in male rats at 2500 
mg/kg/day (7–8%) and 5000 mg/kg/day (8–9%). A decrease in overall feed 
consumption was also observed at 5000 mg/kg/day (8%) in male rats only. 
90-days toxicology experiments revealed that at 3000 mg/kg/day NR 
treatment lead to adverse effects in liver, kidneys, testes, epididymides and 
ovaries. These effects included increases in clinical chemistry parameters 
related to hepatocyte damage (ALT, ALP, and GGT) and a corresponding 
increase in liver weight, centrilobular hepatocellular hypertrophy, and single 
cell necrosis. In addition, thyroid follicular cell hypertrophy and increased 
kidney weight with exacerbation of chronic progressive nephropathy were 


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observed. Statistically significant but minor reductions in sodium and chloride 
were seen and microscopically associated with hypertrophy of zona 
glomerulosa in adrenals at 3000 mg/kg. NR administration at 1000 mg/kg/day 
dose level resulted in treatment-related organ weight changes in liver and 
kidney and increases in neutrophils, ALT and triglycerides, which were 
statistically significant in female rats only. Although these changes were 
considered adverse, based on their dose-dependent responsiveness, the 
increases in ALT and triglycerides occurred only in one gender and were below 
the twofold increase that is typically used as the cut-off for a biologically 
significant effect in the absence of histological results. The kidney weight 
increases at this dose also occurred in the absence of corresponding 
histopathology. Therefore, the liver and kidney effects at 1000 mg/kg/day 
were considered to be treatment related, but mild and potentially adaptive in 
nature due to prolonged exposure to this form of niacin. There were no 
treatment-related adverse effects noted at 300 mg/kg/day, although there 
was a slight decrease (8%) in overall body weight, which was considered 
adaptive. The NOAEL and LOAEL for NR were determined to 300 and 1000 
mg/kg body weight/day, respectively. A UL for human exposure to NR is 
derived by application of a 100-fold safety factor to the NOAEL determined 
from this 90-day study; the UL for NR is 3 mg/kg/day or 180 mg/day, 
assuming a body weight of 60 kg.  
 
In the only published human study of NR, 1000 mg/day was administered to 
a single human subject and increased NAD+ plasma levels up to 2.7 folds. In 
a subsequent experiment in the same study, 12 healthy adults used NR at 100 
mg/day, 300 mg/day and 1000 mg/day single doses with 1 week wash-out 
periods in between. Over the total of 36 days of observation of study 
participants, there were no serious adverse events and no events that were 
dose-dependent. two individuals self-reported flushing at the 300 mg dose but 
not at the 100 mg or 1,000 mg dose, and two individuals self-reported feeling 
hot at the 1,000 mg dose but not at lower doses. 
 
 MRI/MRS Scans: In terms of the MRI and MRS scans, unlike X-rays or CAT 
scans, magnetic resonance (MR) technology does not use ionizing radiation. 
The MR system requires the use of rapidly varying magnetic gradient fields 
and strong radio frequency fields, which conform to the guidelines established 
by the US FDA for time varying magnetic fields in MR devices. This study uses 
a standard clinical MRI scanner (3 Tesla or 3T), as well as a high field (4 Tesla 
or 4T) MRI scanner. The 4T scanner is not used for routine clinical studies in 
children or adults, but the FDA has determined (July 14, 2003) that scanners 
with magnetic field strengths of less than 8 Tesla (double this scanner) or less 
do not represent a significant risk to adults, children, or infants aged more 
than 1 month. There could be adverse effects that are delayed or very mild, 
such that they have not yet been recognized. Most people experience no ill 
effects from 3T or 4T scans, but some people do report claustrophobia (fear 
of being in enclosed small spaces), dizziness, mild nausea, headaches, a 


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metallic taste in their mouth, double vision, or sensation of flashing lights. 
These symptoms, if present, disappear shortly after leaving the scanner. No 
serious adverse effects have been reported to date at any site operating at 3T 
or 4T field strength. 
 
Blood Draw: Blood draw may lead to a small arm bruise and, in rare cases, 
clot or infection at the site the blood was drawn. Some people become light-
headed during or immediately after a blood draw. These are rare occurrences 
and in our experience vast majority of subjects tolerate blood draws well. 
 
Psychiatric Evaluation: In terms of the psychiatric evaluation, some 
subjects might feel uncomfortable answering questions, but they will not be 
forced to answer if they do not wish to do so. The risk of breach of 
confidentiality is present by extremely slight, given the precautions we take 
in de-identifying and protecting our data. 
 
EXPECTED BENEFITS 
Describe both the expected benefits to individual subjects participating in the research and the 
importance of the knowledge that may reasonably be expected to result from the study.  Provide 
a brief, realistic summary of potential benefits to subjects, for example, “It is hoped that the 
treatment will result in a partial reduction in tumor size in at least 25% of the enrolled subjects.”  
Indicate how the results of the study will benefit future patients with the disease/condition being 
studied and/or society, e.g., through increased knowledge of human physiology or behavior, 
improved safety, or technological advances. 
 
Participants are informed that there is no direct benefit to them from 
participating in this study. It is hoped that future patients might benefit if the 
results of the study help to understand the effect of NR on brain metabolism. 
One potential benefit is providing new information to subjects regarding their 
health information. Structural images taken during the 3T research scan will 
be read by a radiologist. Any follow up suggested by the radiologist and clinical 
director of the brain imaging center will be provided at no cost to the subject. 
 
 
EQUITABLE SELECTION OF SUBJECTS 
The risks and benefits of the research must be fairly distributed among the populations that stand 
to benefit from it.  No group of persons, for example, men, women, pregnant women, children, 
and minorities, should be categorically excluded from the research without a good scientific or 
ethical reason to do so.  Please provide the basis for concluding that the study population is 
representative of the population that stands to potentially benefit from this research.
All men and women who meet the study criteria may be approached about 
the study. Subjects of all ethnic and socioeconomic backgrounds are included. 
Therefore, none of the participants are unfairly burdened with risks; nor do 
any populations stand to benefit to a greater degree than others.  
 


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Pregnant and nursing women are excluded from the study as the effects of NR 
and long- term risks of MR exposure to the fetus are unknown. For the 
purposes of this study, subjects who are female and menstruating must be 
sexually inactive or using a contraceptive measure for at least 1 month prior 
to entering the study. These subjects must also have a negative blood 
pregnancy test at study entry and negative urine pregnancy tests prior to each 
MRI/MRS scan. 
 
 
 
When people who do not speak English are excluded from participation in the research, provide 
the scientific rationale for doing so.  Individuals who do not speak English should not be denied 
participation in research simply because it is inconvenient to translate the consent form in 
different languages and to have an interpreter present.
Individuals who do not speak English will not be allowed to participate in this 
study. 
 
 
 
 
For guidance, refer to the following Partners policy: 
          Obtaining and Documenting Informed Consent of Subjects who do not Speak English
          https://partnershealthcare-public.sharepoint.com/ClinicalResearch/Non-
English_Speaking_Subjects.1.10.pdf
 
 
 
RECRUITMENT PROCEDURES 
Explain in detail the specific methodology that will be used to recruit subjects.  Specifically 
address how, when, where and by whom subjects will be identified and approached about 
participation.  Include any specific recruitment methods used to enhance recruitment of women 
and minorities.
For subject recruitment, the research coordinators/assistants will post online 
advertisements and flyers around the McLean campus; describing the study 
and the procedures involved. Participants who call in about the study will go 
through a phone screening process, during which they will be informed that 
everything that is said will remain entirely confidential. If the participants 
screen through, a mutually agreeable interview time will be set up. The 
participants will come in and go through the consent process and be 
administered the Informed Consent by a licensed physician investigator. The 
subject is then provided with a copy of their signed consent form to review 
and keep. 
 
 
 


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Provide details of remuneration, when applicable.  Even when subjects may derive medical 
benefit from participation, it is often the case that extra hospital visits, meals at the hospital, 
parking fees or other inconveniences will result in additional out-of-pocket expenses related to 
study participation.  Investigators may wish to consider providing reimbursement for such 
expenses when funding is available
 
Subjects will be compensated by check in 3-4 weeks for the procedures 
that they complete. The breakdown of compensation is as follows: 
First Part of the Study (total: $230) 
• 
Clinical evaluation: $30/visit 
• 
Blood draw of 30 ml: $15/draw 
• 
Diagnostic MR Scan, CAP protocol (MR Scan at 3T- 1): MRS protocol 
to quantify Glu and GABA at 3T (MR Scan at 3T- 2): $50/scan 
• 
Phosphorous MRS/MT at 4T (MR Scan at 4T- 1): $60/scan 
• 
Diffusion Tensor Spectroscopy (DTS) at 4T (MR Scan at 4T- 2): 
$60/scan 
• 
Transportation: $5/day of visits that take place (x 3) 
Second Part of the Study (total: $120): 
• 
Medication: $5 per day of administration that takes place (x16) 
• 
Transportation: $5/day of visits that take place (x5) 
• 
Blood draw of 30 ml: $15/draw  
Third Part of the Study (total: 225$): 
• 
Clinical evaluation: $30/visit 
• 
Blood draw of 30 ml: $15/draw 
• 
CAP protocol (MR Scan at 3T- 1), MRS protocol to quantify Glu and 
GABA 3T (MR Scan at 3T- 2): $50/scan 
• 
Phosphorous MRS/MT at 4T (MR Scan at 4T- 1): $60/scan 
• 
Diffusion Tensor Spectroscopy (DTS) at 4T (MR Scan at 4T- 2): 
$60/scan 
• 
Transportation: $5/day of visits that take place (x2) 
 
If the subject does not complete the entire study he/she will be 
compensated for the procedures listed above that were completed. The 
subjects will be compensated a total of up to $ 575 for all study procedures. 
If the subject cannot combine the diagnostic MRI scan with the CAP 3T 
scan, he/she will be paid $25 for a freestanding diagnostic scan at the 3T 
scanner. 
If the subject travel to McLean Hospital and is somehow unable to complete 
any part of the study, he/she will be compensated $25 for his/her time and 
travel expenses incurred during the trip here.  
 
 
For guidance, refer to the following Partners policies: 
          Recruitment of Research Subjects 
          https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/Recruitment_Of_Research_Subjects.pdf


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          Guidelines for Advertisements for Recruiting Subjects
          https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/Guidelines_For_Advertisements.1.11.pdf
 
          Remuneration for Research Subjects
          https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/Remuneration_for_Research_Subjects.pdf
 
 
CONSENT PROCEDURES 
Explain in detail how, when, where, and by whom consent is obtained, and the timing of consent 
(i.e., how long subjects will be given to consider participation).  For most studies involving more 
than minimal risk and all studies involving investigational drugs/devices, a licensed physician 
investigator must obtain informed consent.  When subjects are to be enrolled from among the 
investigators’ own patients, describe how the potential for coercion will be avoided.
 
For participants, consent is obtained in a private interview room. The physician 
(Dr. Chouinard, Dr. Baker, Dr. Shinn, Dr. Murphy; one of them will be present 
in each steps of the study according to their availability) and a research 
assistant will thoroughly review the consent form with the participant. 
Subjects are given as much time as they need to look over the consent before 
signing it. If subjects ask for time to consider participating in the study, they 
are given as much time as they need. Typically, the physician and the research 
assistant will check back the next day and/or give the subject a phone number 
to call if the subject is interested in participating. 
 
NOTE: When subjects are unable to give consent due to age (minors) or impaired decision-
making capacity, complete the forms for Research Involving Children as Subjects of Research 
and/or Research Involving Individuals with Impaired Decision-making Capacity, available on 
the New Submissions page on the PHRC website: 
      https://partnershealthcare.sharepoint.com/sites/phrmApply/aieipa/irb 
 
For guidance, refer to the following Partners policy: 
     Informed Consent of Research Subjects:
     https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/Informed_Consent_of_Research_Subjects.pdf
 
 
 
DATA AND SAFETY MONITORING 
Describe the plan for monitoring the data to ensure the safety of subjects.  The plan should 
include a brief description of (1) the safety and/or efficacy data that will be reviewed; (2) the 
planned frequency of review; and (3) who will be responsible for this review and for determining 
whether the research should be altered or stopped.  Include a brief description of any stopping 
rules for the study, when appropriate.  Depending upon the risk, size and complexity of the 


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study, the investigator, an expert group, an independent Data and Safety Monitoring Board 
(DSMB) or others might be assigned primary responsibility for this monitoring activity.        
 
NOTE: Regardless of data and safety monitoring plans by the sponsor or others, the principal 
investigator is ultimately responsible for protecting the rights, safety, and welfare of subjects 
under his/her care. 
 
Subjects are thoroughly screened by a research assistant and a qualified 
physician (Dr. Chouinard; Dr. Baker; Dr. Shinn; Dr. Murphy; one of them will 
be present in each steps of the study according to their availability) prior to 
their enrollment in the study to ensure subject safety. The physician closely 
monitors the participants during the medication period. Subjects are carefully 
assessed before, during, and after the MRI scans by the research assistant 
and MR technologist or authorized personnel to ensure that they suffer no 
adverse reactions. The physician will be present in all phases of the screening 
process. Subjects are carefully assessed before, during, and after the blood 
draw by the research assistant to ensure that they suffer no adverse reactions. 
Participants may experience an emotional reaction in response to the clinical 
evaluation portion of the study; however, this risk is mitigated by the 
investigators' offering the subjects the possibility to take a break or withdraw 
from the study. The PI closely oversees all of the study activities and 
intervenes wherever necessary. 
 
 
Describe the plan to be followed by the Principal Investigator/study staff for review of adverse 
events experienced by subjects under his/her care, and when applicable, for review of sponsor 
safety reports and DSMB reports.  Describe the plan for reporting adverse events to the sponsor 
and the Partners’ IRB and, when applicable, for submitting sponsor safety reports and DSMB 
reports to the Partners’ IRBs.  When the investigator is also the sponsor of the IND/IDE, include 
the plan for reporting of adverse events to the FDA and, when applicable, to investigators at 
other sites.   
 
NOTE: In addition to the adverse event reporting requirements of the sponsor, the principal 
investigator must follow the Partners Human Research Committee guidelines for Adverse Event 
Reporting
As soon as a member of research staff, or the PI, learns of an adverse event, 
he/she will first consider the safety of the participant. If the participant is not 
safe the member of the research staff/PI will take appropriate steps to stabilize 
the subject. Members of the research staff will defer to the PI's judgment. If 
the participant is safe, then the person who learned of the event will call the 
PI and/or other members of the research staff who had contact with the 
participant. They will decide what course of action to take with the participant 
in order to deal with the event. Principal investigator will then submit an 
adverse event report to the PHRC within 5 working days/7 calendar days of 
the date that the investigator first becomes aware of the problem. 
 


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MONITORING AND QUALITY ASSURANCE 
Describe the plan to be followed by the principal investigator/study staff to monitor and assure 
the validity and integrity of the data and adherence to the IRB-approved protocol.  Specify who 
will be responsible for monitoring, and the planned frequency of monitoring.  For example, 
specify who will review the accuracy and completeness of case report form entries, source 
documents, and informed consent.   
 
NOTE: Regardless of monitoring plans by the sponsor or others, the principal investigator is 
ultimately responsible for ensuring that the study is conducted at his/her investigative site in 
accordance with the IRB-approved protocol, and applicable regulations and requirements of the 
IRB.
 
Dost Ongur, the Principal Investigator (PI), will be responsible for monitoring 
the validity and integrity of the data, as well as adherence to the protocol. 
The study coordinator and PI will report any deviations from the protocol 
immediately to the IRB. 
 
 
For guidance, refer to the following Partners policies: 
          Data and Safety Monitoring Plans and Quality Assurance
            https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/DSMP_in_Human_Subjects_Research.pdf  
          
          Reporting Unanticipated Problems (including Adverse Events)
          https://partnershealthcare-
public.sharepoint.com/ClinicalResearch/Reporting_Unanticipated_Problems_including_Adverse_Events.pdf
 
 
 
PRIVACY AND CONFIDENTIALITY 
Describe methods used to protect the privacy of subjects and maintain confidentiality of data 
collected.  This typically includes such practices as substituting codes for names and/or medical 
record numbers; removing face sheets or other identifiers from completed 
surveys/questionnaires; proper disposal of printed computer data; limited access to study data; 
use of password-protected computer databases; training for research staff on the importance of 
confidentiality of data, and storing research records in a secure location.   
 
NOTE: Additional measures, such as obtaining a Certificate of Confidentiality, should be 
considered and are strongly encouraged when the research involves the collection of sensitive 
data, such as sexual, criminal or illegal behaviors.
All subject scans and clinical data are coded with research numbers that do 
not contain any identifying information. The code linking the research number 
to personal identifying information is stored in a password-protected 
encrypted computer file on a locked computer in a locked office at McLean. 
Information about the subjects‟ diagnoses, medical and other relevant study 


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information will be maintained in computers accessible only to the 
investigators and research staff that they designate. The data may be 
maintained for an indefinite period of time since scientific progress may 
indicate that new analyses be carried out on previously obtained data. The 
data will be collected and stored via the secure web-based application 
REDCap. The application complies with HIPAA regulations and will store the 
information securely, protected by web authentication, and Secure Sockets 
Layer (SSL) encryption. Results of the research specific to any subject will not 
be provided to anyone including the subject, except for in the case where the 
subject‟s structural scan is abnormal. In this case, the PI is required to inform 
the subject of the abnormal scan and schedule the necessary follow-ups cans 
at McLean. Blood samples will be encoded and only Dr. Öngür and his research 
staff will have access to the code key. If third-party uses for blood samples 
are planned, we will submit a proposal for such uses for IRB review and 
approval prior to initiating them. The code key linking the sample to personal 
identifiers will never be provided to such third parties and third-party 
investigators will have to agree not to attempt to gain access to such 
identifiers. 
 
 
 
SENDING SPECIMENS/DATA TO RESEARCH COLLABORATORS OUTSIDE 
PARTNERS 
Specimens or data collected by Partners investigators will be sent to research collaborators 
outside Partners, indicate to whom specimens/data will be sent, what information will be sent, 
and whether the specimens/data will contain identifiers that could be used by the outside 
collaborators to link the specimens/data to individual subjects.
 
N/A 
 
 
Specifically address whether specimens/data will be stored at collaborating sites outside 
Partners for future use not described in the protocol.  Include whether subjects can withdraw 
their specimens/data, and how they would do so.  When appropriate, submit documentation of 
IRB approval from the recipient institution.
 
None of the samples will be used for a future use not yet described in the 
protocol, as of now. But science is always changing and such uses may emerge 
in the future. If there was a future use, a request would be submitted to the 
IRB for permission. Subjects can choose to withdraw their sample at any point 
in time from analysis. If a subject wishes to withdraw their sample, they will 
be instructed to write and sign a letter to that effect. 
 
 


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RECEIVING SPECIMENS/DATA FROM RESEARCH COLLABORATORS OUTSIDE 
PARTNERS 
When specimens or data collected by research collaborators outside Partners will be sent to 
Partners investigators, indicate from where the specimens/data will be obtained and whether the 
specimens/data will contain identifiers that could be used by Partners investigators to link the 
specimens/data to individual subjects.  When appropriate, submit documentation of IRB 
approval and a copy of the IRB-approved consent form from the institution where the 
specimens/data were collected.
 
N/A