The Role of the Microbiome in Blood Glucose Regulation in Response to Peanut Consumption
Phase: PHASE2
Conditions: Type2 Diabetes, Cardiovascular Diseases
Sponsor: Penn State University



Page 2 of 29 (V.04/27/2017) 
 
University Park, PA 16802-7014 
Phone: 814-865-1775 
Fax: 814-863-8699 
Email: irb-orp@psu.edu 
Hershey, PA 17033 
(Physical Office Location: Academic Support Building Room 1140) 
Phone: 717-531-5687 
Fax number: 717-531-3937 
Email: irb-hspo@psu.edu 
 
 
Table of Contents 
1.0 
Objectives 
2.0 
Background 
3.0 
Inclusion and Exclusion Criteria 
4.0 
Recruitment Methods 
5.0 
Consent Process and Documentation 
6.0 
HIPAA Research Authorization and/or Waiver or Alteration of Authorization 
7.0 
Study Design and Procedures 
8.0 
Subject Numbers and Statistical Plan 
9.0 
Confidentiality, Privacy and Data Management 
10.0 
Data and Safety Monitoring Plan 
11.0 
Risks 
12.0 
Potential Benefits to Subjects and Others 
13.0 
Sharing Results with Subjects 
14.0 
Subject Stipend (Compensation) and/or Travel Reimbursements 
15.0 
Economic Burden to Subjects 
16.0 
Resources Available 
17.0 
Other Approvals 
18.0 
Multi-Site Research 
19.0 
Adverse Event Reporting 
20.0 
Study Monitoring, Auditing and Inspecting 
21.0 
Future Undetermined Research: Data and Specimen Banking 
22.0 References 

Page 3 of 29 (V.04/27/2017) 
 
Describe the purpose, specific aims or objectives. State the hypotheses to be tested. 
State the primary endpoints to be measured in the study. Clinical trials typically have a primary 
objective or endpoint. Additional objectives and endpoints are secondary. The endpoints (or outcomes), 
determined for each study subject, are the quantitative measurements required by the objectives. 
Measuring the selected endpoints is the goal of a trial (examples: response rate and survival). 
State the secondary endpoints to be measured in the study. 
1.0 
Objectives 
 
1.1 
Study Objectives 
 
The purpose of the study is to evaluate the effects of nighttime peanut consumption (i.e., after dinner 
and before sleep) on fasting blood glucose levels, longer-term blood glucose control, and risk factors for 
cardiovascular disease. Furthermore, this study will investigate the relationship between the microbiota, 
shifts in the microbiota with peanut consumption and the effect on blood glucose regulation. There is 
some emerging evidence that the microbiome predicts glycemic response and this study would provide 
the first robust test of the role of the microbiome in blood glucose regulation in response to peanut 
consumption. 
 
The aims of the study are as follows: 
- To determine the effect of consuming one ounce of peanuts as an evening snack (after dinner and 
before sleep) on glycemic control and risk factors for cardiovascular disease, compared with an 
isocaloric high carbohydrate snack, in people with impaired fasting glucose. 
- To assess changes in the profile of the gut bacterial community in response to the peanut treatment, 
compared with an isocaloric high carbohydrate snack, in people with impaired fasting glucose. 
- To investigate the relationship between markers of glycemic control, after each treatment, and shifts in 
the microbiota to elucidate the role of the microbiome in glucose regulation. 
Hypothesis 
- consuming peanuts as an evening snack will reduce fasting glucose levels compared to an isocaloric 
high carbohydrate control snack. 
- Improvements in fasting glucose levels with peanut consumption will be correlated with favorable 
shifts in the microbiota i.e. peanut consumption will result in enrichment of bacteria known to be 
biomarkers of a healthy gut and these shifts will be associated with the magnitude of blood glucose 
lowering observed. 
 
1.2 
Primary Study Endpoints 
 
Fasting plasma glucose 
 
1.3 
Secondary Study Endpoints 
 
- 
Fructosamine 
- 
Fasting insulin 
- 
Microbiome 
- 
Peripheral and central blood pressure 
- 
Augmentation index 
- 
Pulse wave velocity 
- 
Lipids/lipoproteins 
- 
Weight 
- 
Dietary intake (calorie, macronutrient and overall diet quality). 

Page 4 of 29 (V.04/27/2017) 
 
Describe the scientific background and gaps in current knowledge. 
Describe any relevant preliminary data. 
2.0 
Background 
 
2.1 
Scientific Background and Gaps 
 
Approximately 34% of adults in the U.S. have pre-diabetes[1], defined as impaired fasting glucose or impaired 
glucose tolerance, placing them at substantially higher risk of developing type 2 diabetes[2]. Seventy-five percent 
of middle-aged people with pre-diabetes will develop type 2 diabetes in their lifetime[3]. In addition, individuals 
with pre-diabetes also present with a greater number of cardiovascular risk factors[4] and have a 10-20% higher 
risk of cardiovascular disease[5]. Therefore, it is a public health priority to identify strategies to reduce fasting 
blood glucose in individuals with pre-diabetes to delay the onset of type 2 diabetes. 
A number of observational studies show nut consumption reduces diabetes risk[6-8]. A pooled analysis of five 
prospective cohort studies and one randomized controlled trial showed a 13% reduction in type 2 diabetes risk 
with consumption of 4 servings (28.4 g/serving) of nuts per week[6]. A more recent systematic review and meta- 
analysis of four studies showed that per 28 g/day of peanuts and tree nuts, risk of diabetes mortality was reduced 
by 39%[7]. There is convincing evidence from observational research to show that nuts, including peanuts reduce 
diabetes risk, and this is likely mediated by improvements in blood glucose control. 
The effect of consuming peanuts as an evening snack on fasting glucose levels has not been tested. This is despite 
the clinical observations that fasting blood glucose is lower when nuts or nut butters are consumed in the 
evening. Adding support to these clinical observations is a study showing that a pre-bedtime snack of uncooked 
corn starch (Extend bar), a slow digesting, complex carbohydrate prevented overnight blood glucose excursions 
and reduced fasting blood glucose levels in adults with type 2 diabetes[9]. 
These observations may be explained in part by a blunting of the Dawn Phenomenon. The Dawn Phenomenon 
is characterized by a rise in early morning fasting blood glucose[10]. A present it is thought that the Dawn 
Phenomenon is caused by excessive glucose production by the liver “at dawn”, in the absence of insulin, and 
thus elevations in fasting blood glucose are observed[11]. Identifying successful strategies to counteract this 
physiological effect is of importance because a rise in fasting blood glucose levels of more than 50 mg/dL can 
result in daylong hyperglycemia[12]. Furthermore, the Dawn Phenomenon is not effectively treated by the current 
oral hypoglycemic agents and therefore an opportunity exists to identify an effective strategy to blunt the Dawn 
Phenomenon, a substantial cause of poor glycemic control[13], and improve overall glycemic control. 
Emerging evidence suggests that the microbiome may determine glycemic response. Large individual variation 
has been observed in glycemic response to foods differing in glycemic index[14], and this has largely been poorly 
understood. However, recently, a one-week randomized controlled trial of two different bread treatments 
showed that the glycemic response to the bread type could be predicted based on the microbiome[15]. This paper, 
published in Cell Metabolism (impact factor 18.16), provides some of the first evidence that the microbiome may 
mediate glycemic response. Although this study was only one week long so changes in the microbiome could not 
be detected. Therefore, we propose to conduct a 6 week study to allow investigation of: 1) the effect of the 
microbiome on glycemic response to peanuts vs. the control snack; and 2) how changes in the microbiome in 
response to peanut consumption correlate with changes in glucose regulation. 
Recent data suggests that tree nut consumption for between three and six weeks changes the microbiome[16-19]; 
no studies have assessed the effect of peanuts on the microbiome. In many of these studies there were changes 
in the relative abundance of microbiota known to be associated with beneficial health effects. 
 
2.2 
Previous Data 
 
Previous meal studies from our lab and others have demonstrated that consumption of peanuts with a meal 
reduces post-meal blood glucose levels. In a study led by Dr. Kris-Etherton, blood glucose levels were lower 4 
hours after consumption of a high-saturated fat beverage with 3 oz. of peanuts, compared to a high-saturated 

Page 5 of 29 (V.04/27/2017) 
 
Provide the scientific rationale for the research. 
Create a numbered list below in sections 3.1 and 3.2 of criteria subjects must meet to be eligible for study 
enrollment (e.g., age, gender, diagnosis, etc.). Indicate specifically whether you will include any of the 
following vulnerable populations: (You may not include members of these populations as subjects in your 
research unless you indicate this in your inclusion criteria.) Review the corresponding checklists to ensure that 
you have provided the necessary information. 
• 
Adults unable to consent 
fat beverage with 42 g of an oil blend reflecting the fatty acid composition of the peanut beverage[20]. In a similar 
study, it was shown that consuming peanuts with a high glycemic index (GI) meal improved 60-minute blood 
glucose response by 60% compared to the control in healthy subjects[21]. There is also evidence showing that the 
addition of peanuts to a meal improves blood glucose response to the subsequent meal. Reis et al.[22] reported 
that adding 42.5 g (1.5oz) of peanuts or peanut butter to a breakfast meal improved second meal blood glucose 
levels in obese women. These studies suggest that peanuts or peanut butter have a favorable effect on 
postprandial glucose levels. 
There is also a growing body of evidence showing that nut consumption improves longer term glycemic control 
and risk factors for cardiovascular disease[23]. A meta-analysis of 12 randomized controlled trials, showed that 
tree nut consumption reduced fasting blood glucose in individuals with type 2 diabetes by 0.15 mmol/L after 
approximately 8 weeks[24]. We recently updated this meta-analysis and included all studies examining the effect 
of tree nuts and peanuts in adults (unpublished). Overall, there were improvements in insulin resistance and 
fasting insulin with nut consumption. A trend towards improvements in fasting blood glucose with nut 
consumption was also observed. In this review, five randomized controlled trials were identified that assessed 
the effect of peanuts on blood glucose levels, and these studies were heterogeneous in design, however in all of 
the studies the timing of peanut consumption was not controlled. We hypothesize that nighttime consumption 
of peanuts will result in improvements in fasting glucose levels based on known physiology and research 
demonstrating the glycemic benefit of evening consumption of healthful snacks. 
 
2.3 
Study Rationale 
 
There has been limited investigation of the influence of peanuts on fasting blood glucose, however based on the 
effects of peanuts and peanut butter on other markers of diabetes control including post-prandial blood glucose 
and circulating insulin levels, there is biologic plausibility for this hypothesis. Many of the studies that have been 
conducted have included healthy populations[25-27], and these findings cannot be generalized to people with pre- 
diabetes due to the poor glycemic regulation present in pre-diabetes. In addition, not all of the studies done to 
date have included nutrition counseling on timing and serving sizes of nuts added to the diet[26, 28]. We hypothesize 
that consumption of peanuts in the evening (after dinner and before sleep) will have a greater impact on fasting 
glucose than consumption at other times of the day. This is because peanuts and peanut butter are rich in MUFA, 
which delay gastric emptying and promote a slow and sustained release of carbohydrate that may act to stabilize 
overnight blood glucose levels and reduce the spike in glucose levels seen in the early morning, which makes 
subsequent glucose control throughout the day challenging. 
The proposed project will generate high quality robust data in a cohort with pre-diabetes for: 1) the effect of 
consuming one ounce of peanuts as an evening snack (after dinner and before sleep) on glycemic control and risk 
factors for cardiovascular disease, compared with an isocaloric high carbohydrate snack; 2) changes that occur in 
the profile of the gut bacterial community in response to peanut consumption compared with an isocaloric high 
carbohydrate snack; 3) the relationship between markers of glycemic control and shifts in the microbiota in 
response to peanut consumption to elucidate the role of the microbiome in glucose regulation. 
 
 
3.0 
Inclusion and Exclusion Criteria 
 

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List the criteria that define who will be included in your study. 
List the criteria that define who will be excluded in your study. 
Insert subject withdrawal criteria (e.g., safety reasons, failure of subject to adhere to protocol 
requirements, subject consent withdrawal, disease progression, etc.). 
 
 
3.1 
Inclusion Criteria 
 
Participants will be non-smoking males and females aged 18 to 75 years with impaired fasting glucose at 
screening (≥ 100 mg/dL). Participants will have a BMI ≥20 and ≤40 kg/m2. 
 
3.2 
Exclusion Criteria 
 
We will not recruit participants who have chronic disease risk factors that are diagnostic of diabetes 
(fasting glucose > 126 mg/dL) or hypertension (SBP >160 mm Hg or DBP > 100 mm Hg). In addition, they 
will not be taking anti-hypertensive, lipid lowering or glucose lowering drugs. Individuals with 
established CVD, stroke, diabetes, liver, kidney, autoimmune diseases or inflammatory conditions such 
as gastrointestinal disorders or rheumatoid arthritis will not be eligible. Other exclusion criteria will 
include: use of supplements (psyllium, fish oil, soy lecithin, and phytoestrogens) and botanicals and not 
willing to cease for the duration of the study; women who are pregnant, lactating, planning to become 
pregnant or have given birth in the past year; weight loss of ≥10% of body weight within the 6 
months prior to enrolling in the study; or smoking or use of any tobacco products in past 6 months. 
Participants with an allergy/intolerance/sensitivity to test foods will be excluded (i.e. peanuts, gluten, 
grain products, cheese). Individuals consuming >14 alcoholic drinks/week or not willing to avoid alcohol 
consumption for 48 hour prior to test visit will be ineligible for the study. 
 
3.3 
Early Withdrawal of Subjects 
 
3.3.1 Criteria for removal from study 
 
Failure to comply with study procedures. 
Participant withdraws consent. 
o Review “CHECKLIST: Cognitively Impaired Adults (HRP-417)” to ensure that you have 
provided sufficient information. HRP-417 can be accessed by clicking the Library link in 
CATS IRB (http://irb.psu.edu). 
• 
Individuals who are not yet adults (infants, children, teenagers) 
o 
If the research involves persons who have not attained the legal age for consent to 
treatments or procedures involved in the research (“children”), review the “CHECKLIST: 
Children (HRP-416)” to ensure that you have provided sufficient information. HRP-416 
can be accessed by clicking the Library link in CATS IRB (http://irb.psu.edu). 
• 
Pregnant women 
o 
Review “CHECKLIST: Pregnant Women (HRP-412)” to ensure that you have provided 
sufficient information. HRP-412 can be accessed by clicking the Library link in CATS IRB 
(http://irb.psu.edu). 
• 
Prisoners 
o 
Review “CHECKLIST: Prisoners (HRP-415)” to ensure that you have provided sufficient 
information. HRP-415 can be accessed by clicking the Library link in CATS IRB 
(http://irb.psu.edu). 
• 
Neonates of uncertain viability or non-viable neonates 
o 
Review “CHECKLIST: Neonates (HRP-413)” or “CHECKLIST: Neonates of Uncertain Viability 
(HRP-414)” to ensure that you have provide sufficient information. HRP-413 and HRP-414 
can be accessed by clicking the Library link in CATS IRB (http://irb.psu.edu). 

Page 7 of 29 (V.04/27/2017) 
 
Describe when and how to withdraw subjects from the study; the type and timing of the data to 
be collected for withdrawal of subjects; whether and how subjects are to be replaced; the 
follow-up for subjects withdrawn from investigational treatment. 
Describe the methods that will be used to identify potential subjects or the source of the subjects. If not 
recruiting subjects directly (e.g., database query for eligible records or samples) state what will be 
queried, how and by whom. 
StudyFinder: If you intend to use StudyFinder (http://studyfinder.psu.edu) for recruitment purposes, 
please indicate this in section 4.1 along with any other methods for identifying subjects. Note that 
information provided in this protocol should be consistent with information provided on the 
StudyFinder page in your CATS IRB study. 
For Penn State Hershey submissions using Enterprise Information Management (EIM) for recruitment, 
attach your EIM Design Specification form on the Basic Information page in CATS IRB 
(http://irb.psu.edu). See HRP-103 Investigator Manual, “What is appropriate for study recruitment?” for 
additional information. 
Describe how, where and when potential subjects will be recruited (e.g., approaching or providing 
information to potential subjects for participation in this research study). 
3.3.2 
Follow-up for withdrawn subjects 
 
No safety concerns; no reason for follow-up. If consent is withdrawn no data from the 
participant will be used. Otherwise, if consent is not withdrawn, data from individuals who 
withdraw from the study may be used in an intent-to-treat analysis but another individual will 
be enrolled to ensure that an adequate sample size (with complete data) is reached. 
 
4.0 
Recruitment Methods 
 
4.1 
Identification of subjects 
 
Flyer/posters will be placed in campus buildings and facilities as well as the surrounding area (gyms, 
churches, supermarkets, coffee shops etc.) to identify potential subjects residing in and around the State 
College. Ads will also be placed in the local papers, magazines (e.g Centre Daily Times) and coupon 
mailers (e.g. Valpak), which are distributed to residential homes. In addition, radio ads will be run. 
Websites (e.g. http://clinicaltrials.gov/, Facebook, Craig's List), and PSU listservs will be used to advertise 
the study. We also will contact individuals who have participated in previous studies and indicated to 
our research group that they are interested in participating in future studies. A letter to local businesses 
or organization may be utilized requesting they share study details with their members/employees if 
permitted. 
4.2 
Recruitment process 
 
Public advertisements (flyers/posters/ newspaper ads/circulars/ websites and social media/ radio) in the 
local community (State College/ University Park area) will be used to recruit people. These ads will be 
run periodically depending on recruitment. When an individual responds to an ad, study staff will 
contact the individual using the contact details provided. 
 
A letter to local businesses or organization may be utilized requesting they share study details with their 
members/employees if permitted. 
 
All of these methods of recruitment will be used until the target sample size is reached. 

Page 8 of 29 (V.04/27/2017) 
 
List the materials that will be used to recruit subjects. Add recruitment documents to your study in CATS 
IRB (http://irb.psu.edu) on the “Consent Forms and Recruitment Materials” page. For advertisements, 
upload the final copy of printed advertisements. When advertisements are taped for broadcast, attach 
the final audio/video tape. You may submit the wording of the advertisement prior to taping to preclude 
re-taping because of inappropriate wording, provided the IRB reviews the final audio/video tape. 
StudyFinder: If you intend to use StudyFinder (http://studyfinder.psu.edu) for recruitment purposes, 
you do not need to upload a separate recruitment document for information placed on the StudyFinder 
site to your study in CATS IRB. Necessary information will be captured on the StudyFinder page in your 
CATS IRB study. 
If potential subjects will be asked eligibility questions before obtaining informed consent, describe the 
process. Add the script documents and a list of the eligibility questions that will be used to your study in 
CATS IRB (http://irb.psu.edu) on the “Consent Forms and Recruitment Materials” page. 
StudyFinder: If you intend to use StudyFinder (http://studyfinder.psu.edu) for recruitment purposes, 
any scripts (phone, email, or other) used when contacting StudyFinder participants as well as any 
eligibility screening questions must be added to your study in CATS IRB (http://irb.psu.edu) on the 
“Consent Forms and Recruitment Materials” page. 
Refer to “SOP: Informed Consent Process for Research (HRP-090)”, for information about the process of 
obtaining informed consent from subjects. HRP-090 can be accessed by clicking the Library link in CATS IRB 
(http://irb.psu.edu). 
4.3 
Recruitment materials 
 
Flyer and print ad (used for Newspaper and Magazine advertisement, circular ads, websites) 
PSU Newswire, email, or list-serve advertisement 
Letter: a letter to local businesses or organizations may be utilized requesting they share study details 
with their members/employees. 
Radio ad 
 
4.4 
Eligibility/screening of subjects 
 
Potential subjects who have responded to advertisements will be asked eligibility questions via a 
telephone screening before informed consent is obtained (refer to telephone screening form for 
complete list of screening questions). If you do not qualify for the study, the general reason why 
you did not qualify for the study will be recorded under an assigned screening study ID#. 
Documents containing information gathered during the telephone screening will be stored in a 
locked cabinet in 317 Chandlee lab or in a password protected file on a secure network. If you 
do qualify for the study, information gathered during the telephone screening such as names, 
addresses, telephone numbers, email addresses, date of birth, and visit dates will be linked to 
data via a code break list. Once enrolled in the study, all data collection will be performed 
under an assigned study ID# that is known only to the principal investigators, study 
coordinators and CRC staff (for purposes of blood collection and safety). These are the only 
persons able to connect the participant's identifiable information. 
 
5.0 
Consent Process and Documentation 
 
 
5.1 
Consent Process 

Page 9 of 29 (V.04/27/2017) 
 
Describe where and when the consent process will take place. 
Describe the steps that will be taken to minimize the possibility of coercion or 
undue influence in the consent process. 
If you are requesting a waiver or alteration of consent (consent will not be obtained, required 
information will not be disclosed, or the research involves deception), describe the rationale 
for the request in this section. If the alteration is because of deception or incomplete 
disclosure, explain whether and how subjects will be debriefed. Add any debriefing materials or 
document(s) to your study in CATS IRB (http://irb.psu.edu) on the “Supporting Documents” 
page. NOTE: Review the “CHECKLIST: Waiver or Alteration of Consent Process (HRP-410)” to 
ensure you have provided sufficient information for the IRB to make these determinations. 
HRP-410 can be accessed by clicking the Library link in CATS IRB (http://irb.psu.edu). 
Refer to “SOP: Written Documentation of Consent (HRP-091)” for information about the process 
to document the informed consent process in writing. HRP-091 can be accessed by clicking the 
Library link in CATS IRB (http://irb.psu.edu). 
If you will document consent in writing, describe how consent of the subject will be documented 
in writing. Add the consent document(s) to your study in CATS IRB (http://irb.psu.edu) on the 
“Consent Forms and Recruitment Materials” page. Links to Penn State’s consent templates are 
available in the same location where they are uploaded and their use is required. 
5.1.1 Obtaining Informed Consent 
 
5.1.1.1 Timing and Location of Consent 
 
After a brief telephone conversation explaining the study and answering some 
preliminary screening questions, a screening appointment will be scheduled at 
the Clinical Research Center (CRC). At this appointment, before any procedures 
take place, potential participants will be given the informed consent document. 
Following standard protocol procedure, a trained staff person will review the 
information in detail, make sure the individual understands the study and 
answers any questions they may have. If the participant is still interested in 
continuing with the screening process, both the participant and the staff 
member will sign and date the document. A copy of the sign consent document 
will be provided to the participant. 
 
5.1.1.2 Coercion or Undue Influence during Consent 
 
Study staff, coordinators, and investigators who are fully trained in the 
recruiting process will respond to potential participants during recruitment so as 
to avoid any coercion or undue influence. 
 
5.1.2 Waiver or alteration of the informed consent requirement 
 
Not applicable 
 
5.2 
Consent Documentation 
 
5.2.1 
Written Documentation of Consent 
 
At their scheduled screening clinic appointment, before any procedures take place, potential 
participants will be given the informed consent document. Trained research personnel will 
make sure the individual understands the study expectations and will answer any questions they 

Page 10 of 29 (V.04/27/2017) 
 
If you will obtain consent (verbal or implied), but not document consent in writing, describe how 
consent will be obtained. Add the consent script(s) and/or information sheet(s) to your study in 
CATS IRB (http://irb.psu.edu) on the “Consent Forms and Recruitment Materials” page. Links to 
Penn State’s consent templates are available in the same location where they are uploaded and 
their use is required. Review “CHECKLIST: Waiver of Written Documentation of Consent (HRP- 
411)” to ensure that you have provided sufficient information. HRP-411 can be accessed by 
clicking the Library link in CATS IRB (http://irb.psu.edu). 
If your research presents no more than minimal risk of harm to subjects and involves no 
procedures for which written documentation of consent is normally required outside of the 
research context, the IRB will generally waive the requirement to obtain written documentation 
of consent. 
Indicate what language(s) other than English are understood by prospective subjects or 
representatives. 
 
If subjects who do not speak English will be enrolled, describe the process to ensure that the 
oral and written information provided to those subjects will be in that language. Indicate the 
language that will be used by those obtaining consent. 
 
Indicate whether the consent process will be documented in writing with the long form of the 
consent documentation or with the short form of the consent documentation. Review the 
“SOP: Written Documentation of Consent (HRP-091)” and the “Investigator Manual (HRP-103)” 
to ensure that you have provided sufficient information. HRP-091 and HRP-103 can be accessed 
by clicking the Library link in CATS IRB (http://irb.psu.edu). 
Refer to “CHECKLIST: Cognitively Impaired Adults (HRP-417)” for information about research 
involving cognitively impaired adults as subjects. HRP-417 can be accessed by clicking the Library 
link in CATS IRB (http://irb.psu.edu). 
Describe the process to determine whether an individual is capable of consent. 
may have. If the participant still is interested in continuing with the screening process, both the 
participant and the staff member will sign and date the document. A copy of the consent 
document will be provided to the participant. Signed original copies will be kept on file by the PI. 
 
5.2.2 
Waiver of Documentation of Consent (Implied consent, Verbal consent, etc.) 
 
Verbal consent to participant in the telephone screening will be obtained. The telephone 
screening involves minimal risk and involves no procedures for which written documentation of 
consent is normally required outside of the research context. The questions asked are only 
those needed to ascertain whether a person may be eligible for the study and include contact 
details, and yes or no responses to a number of questions about dietary habits, food allergies, 
medical history and lifestyle. Thus, the only risk is that of minor discomfort when being asked 
questions related to lifestyle and personal medical history. 
5.3 
Consent – Other Considerations 
 
5.3.1 
Non-English Speaking Subjects 
 
Not applicable 
 
5.3.2 
Cognitively Impaired Adults 
 
5.3.2.1 Capability of Providing Consent 

Page 11 of 29 (V.04/27/2017) 
 
Describe whether and how informed consent will be obtained from the legally 
authorized representative. Describe who will be allowed to provide informed 
consent. Describe the process used to determine these individual’s authority to 
consent to research. 
For research conducted in the state, review “SOP: Legally Authorized 
Representatives, Children and Guardians (HRP-013)” to be aware of which 
individuals in the state meet the definition of “legally authorized 
representative”. HRP-013 can be accessed by clicking the Library link in CATS IRB 
(http://irb.psu.edu). 
For research conducted outside of the state, provide information that describes 
which individuals are authorized under applicable law to consent on behalf of a 
prospective subject to their participation in the procedure(s) involved in this 
research. One method of obtaining this information is to have a legal counsel or 
authority review your protocol along with the definition of “children” in “SOP: 
Legally Authorized Representatives, Children, and Guardians (HRP-013).” HRP- 
013 can be accessed by clicking the Library link in CATS IRB (http://irb.psu.edu). 
Describe the process for assent of the subjects. Indicate whether assent will be 
required of all, some or none of the subjects. If some, indicate which subjects will 
be required to assent and which will not. 
If assent will not be obtained from some or all subjects, provide an explanation of 
why not. 
Describe whether assent of the subjects will be documented and the process to 
document assent. The IRB allows the person obtaining assent to document assent 
on the consent document and does not routinely require assent documents and 
does not routinely require subjects to sign assent documents. 
Describe whether and how parental permission will be obtained. If permission 
will be obtained from individuals other than parents, describe who will be 
allowed to provide permission. Describe the process used to determine these 
individual’s authority to consent to each child’s general medical care. 
For research conducted in the state, review “SOP: Legally Authorized 
Representatives, Children and Guardians (HRP-013)” to be aware of which 
individuals in the state meet the definition of “children”. HRP-013 can be 
accessed by clicking the Library link in CATS IRB (http://irb.psu.edu). 
Not applicable. 
 
5.3.2.2 Adults Unable To Consent 
 
Not applicable. 
 
5.3.2.3 Assent of Adults Unable to Consent 
 
Not applicable. 
 
5.3.3 
Subjects who are not yet adults (infants, children, teenagers) 
 
5.3.3.1 Parental Permission 

Page 12 of 29 (V.04/27/2017) 
 
Indicate whether assent will be obtained from all, some, or none of the children. If 
assent will be obtained from some children, indicate which children will be 
required to assent. When assent of children is obtained describe whether and how 
it will be documented. 
This section is about the access, use or disclosure of Protected Health Information (PHI). PHI is individually 
identifiable health information (i.e., health information containing one or more 18 identifiers) that is transmitted 
or maintained in any form or medium by a Covered Entity or its Business Associate. A Covered Entity is a health 
plan, a health care clearinghouse or health care provider who transmits health information in electronic form. 
See the “Investigator Manual (HRP-103)” for a list of the 18 identifiers. HRP-103 can be accessed by clicking the 
Library link in CATS IRB (http://irb.psu.edu). 
If requesting a waiver/alteration of HIPAA authorization, complete sections 6.2 and 6.3 in addition to section 
6.1. The Privacy Rule permits waivers (or alterations) of authorization if the research meets certain conditions. 
Include only information that will be accessed with the waiver/alteration. 
 
 
Not applicable. 
 
5.3.3.2 Assent of subjects who are not yet adults 
 
Not applicable. 
 
6.0 
HIPAA Research Authorization and/or Waiver or Alteration of Authorization 
 
 
6.1 
Authorization and/or Waiver or Alteration of Authorization for the Uses and Disclosures of PHI 
 
Check all that apply: 
X 
Not applicable, no identifiable protected health information (PHI) is accessed, used or 
disclosed in this study. [Mark all parts of sections 6.2 and 6.3 as not applicable] 
 
Authorization will be obtained and documented as part of the consent process. [If this is the 
only box checked, mark sections 6.2 and 6.3 as not applicable] 
 
Partial waiver is requested for recruitment purposes only (Check this box if patients’ medical 
records will be accessed to determine eligibility before consent/authorization has been 
obtained). [Complete all parts of sections 6.2 and 6.3] 
 
Full waiver is requested for entire research study (e.g., medical record review studies). 
[Complete all parts of sections 6.2 and 6.3] 
 
Alteration is requested to waive requirement for written documentation of authorization 
(verbal authorization will be obtained). [Complete all parts of sections 6.2 and 6.3] 
For research conducted outside of the state, provide information that describes 
which persons have not attained the legal age for consent to treatments or 
procedures involved in the research, under the applicable law of the jurisdiction 
in which research will be conducted. One method of obtaining this information 
is to have a legal counsel or authority review your protocol along with the 
definition of “children” in “SOP: Legally Authorized Representatives, Children, 
and Guardians (HRP-013).” HRP-013 can be accessed by clicking the Library link 
in CATS IRB (http://irb.psu.edu). 

Page 13 of 29 (V.04/27/2017) 
 
Include the following statement as written – DO NOT ALTER OR DELETE unless this 
section is not applicable because the research does not involve a waiver of 
authorization. If the section is not applicable, remove the statement and indicate 
as not applicable. 
Describe the plan to destroy the identifiers at the earliest opportunity consistent 
with the conduct of the research. Include when and how identifiers will be 
destroyed. If identifiers will be retained, provide the legal, health or research 
justification for retaining the identifiers. 
By submitting this study for review with a waiver of authorization, you agree to the following statement 
– DO NOT ALTER OR DELETE unless this section is not applicable because the research does not involve a 
waiver or alteration of authorization. If the section is not applicable, remove the statement and indicate 
as not applicable. 
Describe and explain the study design. 
6.2 
Waiver or Alteration of Authorization for the Uses and Disclosures of PHI 
 
6.2.1 
Access, use or disclosure of PHI representing no more than a minimal risk to the privacy of the 
individual 
6.2.1.1 Plan to protect PHI from improper use or disclosure 
 
Not applicable 
 
6.2.1.2 Plan to destroy identifiers or a justification for retaining identifiers 
 
Not applicable 
 
6.2.2 
Explanation for why the research could not practicably be conducted without access to and 
use of PHI 
 
 
Not applicable 
 
6.2.3 
Explanation for why the research could not practicably be conducted without the waiver or 
alteration of authorization 
 
 
Not applicable 
 
6.3 
Waiver or alteration of authorization statements of agreement 
 
Not applicable 
7.0 
Study Design and Procedures 
 
7.1 
Study Design 
Provide an explanation for why the research could not practicably be conducted without the 
waiver or alternation of authorization. 
Provide an explanation for why the research could not practicably be conducted without access 
to and use of PHI. 

Page 14 of 29 (V.04/27/2017) 
 
Provide a description of all research procedures being performed and when they are being performed 
(broken out by visit, if applicable), including procedures being performed to monitor subjects for safety 
or minimize risks. Include any long-term follow-up procedures and data collection, if applicable. 
Describe where or how you will be obtaining information about subjects (e.g., medical records, school 
records, surveys, interview questions, focus group topics, audio or video recordings, data collection 
forms, and collection of specimens through invasive or non-invasive procedures to include the amount 
to be collected and how often). Add any data collection instruments that will be seen by subjects to your 
study in CATS IRB (http://irb.psu.edu) in the “Supporting Documents” page. 
Provide a description as defined above and format accordingly. 
Provide a description as defined above and format accordingly. 
A two-period randomized crossover trial will be conducted. Participants will be randomized to receive 
each treatment for 6 weeks followed by a minimum 4-week wash-out period. During the peanut 
treatment, participants will consume one ounce per day (28 g) of peanuts as an evening snack. The 
control treatments will be an isocaloric high carbohydrate snack (crackers + spread) consumed after the 
evening meal. The peanuts and control foods will be provided to the participants every two weeks 
during the treatment periods; these foods will be purchased from one of the local supermarkets. 
Participants will be given instructions about when to consume the foods. 
 
Fasting blood glucose, fructosamine, insulin, weight, lipids and lipoproteins, central and peripheral blood 
pressure and arterial stiffness will be measured at the beginning and the end of each treatment period. 
Fecal samples will be provided at the beginning and the end of each treatment period for assessment of 
the microbiome. A 24-hour dietary recall will be completed at the beginning and end of each diet to 
determine how consuming the evening snack influences overall dietary intake (including calorie and 
macronutrient intake and overall diet quality). 
7.2 
Study Procedures 
 
7.2.1 
EXAMPLE: Visit 1 or Day 1 or Pre-test, etc. (format accordingly) 
 
Screening: The clinical visit will consist of filling out forms (informed consent, medical history, 
personal information); measuring height and weight so that BMI can be calculated; 
and measuring blood pressure to determine eligibility. If blood pressure is >140/90 mmHg at 
screening the individual will require written approval from their Primary Care Physician prior to 
enrolling the study. Women of child bearing potential will provide a urine sample for a 
pregnancy test. If after these measurements, it is determined that the subject is still eligible, a 
blood sample will be taken and a complete blood count, including liver and kidney function and 
a blood lipid panel will be performed (approximately 19 mls of blood or ~1.25 tablespoon will be 
taken). If the initial blood draw is unsuccessful it may need to be repeated, with permission from 
the participant. In addition, if a potential participant takes thyroid medicine they must provide a 
current (within 6 months) lab test. If they do not have one, an extra 3.5 ml (0.2 Tbsp) of blood 
will be taken to conduct a thyroid test. If all eligibility criteria are met, participants will be 
scheduled for their baseline measurements. Baseline visits typically occur within 1-2 weeks 
following the screening appointment. 
 
7.2.2 
EXAMPLE: Visit 2 or Day 2 or Post-test, etc. (format accordingly) 
 
Baseline and endpoint visits (8 total): 
At the beginning and end of each diet period, two fasting blood samples will be collected 
(separated by at least 24 hours) for analysis of biochemical endpoints. Body weight will be taken 

Page 15 of 29 (V.04/27/2017) 
 
Describe the duration of an individual subject’s participation in the study. 
and vascular health assessments using the SphygmoCor will be performed at the beginning and 
end of each diet period. Participants will also complete a fecal collection at the beginning and 
end of each treatment period. Participants will complete a 24-hour dietary recall at the 
beginning and end of each treatment period. 
 
Plasma/serum analysis: In addition to the blood taken at screening, 12 hour fasting blood 
samples also will be taken on two consecutive days at the beginning and end of each treatment 
period for a total of 8 times. Approximately 60 ml (about 4 Tbsp) will be collected across the two 
visits (30 ml per day). A typical American Red Cross blood donation is 1 pint (500 ml). Blood may 
be analyzed for the following: blood lipids and lipoproteins, glucose and insulin, and 
Fructosamine. 
Central Blood Pressure and Augmentation Index: Following a 5-minute rest period, brachial 
artery systolic and diastolic blood pressure will be measured in the left arm using an automated 
blood pressure cuff. The cuff will reinflate and obtain a pulse wave form. Central blood pressure 
and wave reflection characteristics (augmentation index) will then be derived from the pressure 
waveforms using a validated transfer function with a SphygmoCor System (AtCor Medical, 
Sydney, Australia). This test will be performed in triplicate. 
 
Pulse Wave Velocity: Arterial stiffness will be assessed by calculating the pulse wave velocity 
(PWV) between the carotid and femoral arteries while in the supine position. A cuff will be 
placed on the participant's thigh. The cuff will inflate during the test to record the pulse 
waveform in the femoral artery. A simultaneous measurement of the carotid artery pressure 
waveform will be obtained by an applanation tonometry sensor manually held in place above 
the carotid artery. PWV will subsequently be calculated by dividing the linear distance between 
the carotid and femoral sites by the transit time using the SphygmoCor system (AtCor Medical, 
Sydney Australia). This measurement will be performed in triplicate. 
 
Fecal collection: At the beginning and end of each treatment period, participants will be asked 
to collect a stool sample (~50 g). They will be provided with a stool sample kit and detailed 
instructions for collection of a clean sample. 
 
Dietary intake: The 24-hour recall will be administered through the Automated Self 
Administered 24-Hour (ASA24®) Dietary Assessment Tool. This is an online system where 
participants will provide information about all foods, beverages and supplements consumed 
during the previous day. No identifying information is uploaded to this system, participant ID 
numbers are used to identify the 24-hour records. Participants will have the option of the 
completing the 24-hour recall at home or at the visit. This system generates food group and 
nutrient data from the 24- hour recalls. These data will be used for calculation of diet quality. 
Daily monitoring form: Participants will complete daily monitoring forms regarding 
consumption of test foods, changes in medication or health during the study. When they pick up 
their tests food biweekly, they will be provided with the daily monitoring forms and asked to 
return the completed forms the next time they pick up food. 
 
7.3 
Duration of Participation 
 
Each participant will be involved in the study for approximately 16 weeks; two treatment periods each 
lasting 6 weeks, separated by a ≥ 4 week break. Participants will be expected to pick up the test foods 

Page 16 of 29 (V.04/27/2017) 
 
Indicate the total number of subjects to be accrued. 
If applicable, distinguish between the number of subjects who are expected to be enrolled and 
screened, and the number of subjects needed to complete the research procedures (i.e., numbers of 
subjects excluding screen failures.) 
If applicable, provide a justification of the sample size outlined in section 8.1 – to include reflections on, 
or calculations of, the power of the study. 
Describe the statistical methods (or non-statistical methods of analysis) that will be employed. 
biweekly at the diet center on campus. At the beginning and end of each diet period, data collection 
(described above) will occur. 
Total time for study visits, after the initial screening is approximately 6 hours. Times may vary and 
females will require an additional 5 minutes for a urine pregnancy test a baseline and the end of each 
diet period. The following is an estimate of the amount of time participants will spend in study activities: 
 
■ 
Screening appointment: 
Day 1: Forms, blood pressure, weight, height, blood draw – 45-60 minutes 
(pregnancy testing: females only – 5 minutes) 
■ 
Beginning of treatment period 1 and 2 
Day 1: blood draw, weight, PWA, PWV – 60 minutes 
(pregnancy testing: females only – 5 minutes) 
Day 2: blood draw – 30 minutes 
■ 
End of treatment period 1 and 2: 
Day 1: blood draw, weight, PWA, PWV – 60 minutes 
(pregnancy testing: females only – 5 minutes) 
Day 2: blood draw – 30 minutes 
■ 
Picking up food, fecal collections, and completing 24-hour diet recalls : ~ 5 hours 
Total time for clinic and diet center visits from the beginning to the end of the study ~11 hours 
 
8.0 
Subject Numbers and Statistical Plan 
 
8.1 
Number of Subjects 
 
Approximately 135 subjects will complete the screening process for this study; of those we anticipate 59 
subjects to be eligible A total of 45 participants will complete the study. To achieve this, we will likely 
need to randomize 59 subjects assuming a 30% drop out rate. 
8.2 
Sample size determination 
 
To provide 80% power (p<0.05) to detect a minimum 10 mg/dL difference in fasting glucose between 
the treatments, 45 participants are required (standard deviation of 23.4mg/dL). To account for a 30% 
drop-out rate, 59 subjects will be randomized. Completion of 45 subjects will also provide 80% power 
(p<0.05) to detect a minimum 11 mg/dL (standard deviation 25.9 mg/dL) difference between the 
treatment in LDL-cholesterol, and a 4.5 mmHg difference in systolic blood pressure (standard deviation 
11 mmHg). 
 
8.3 
Statistical methods 

Page 17 of 29 (V.04/27/2017) 
 
For research being conducted at Penn State Hershey or by Penn State Hershey researchers only, the research 
data security and integrity plan is submitted using “HRP-598 – Research Data Plan Review Form Application 
Supplement”, which is available in the Library in CATS IRB (http://irb.psu.edu). Refer to Penn State College of 
Medicine IRB’s “Standard Operating Procedure Addendum: Security and Integrity of Human Research Data”, 
which is available on the IRB’s website. In order to avoid redundancy, for this section state “See the Research 
Data Plan Review Form” in section 9.0 if you are conducting Penn State Hershey research and move on to 
section 10. 
For all other research, in the sections below, describe the steps that will be taken to secure the data during 
storage, use and transmission. 
List the identifiers that will be included or associated with the data and/or specimens in any way 
(e.g., names, addresses, telephone/fax numbers, email addresses, dates (date of birth, 
admission/discharge dates, etc.), medical record numbers, social security numbers, health plan 
beneficiary numbers, etc.). 
 
If no identifiers will be included or associated with the data in any way, whether directly or 
indirectly, please indicate this instead. 
The normality of the data will be tested before performing analyses, and transformations will be made if 
needed. Mixed effect models will be used to determine between-group changes over time and between 
group differences in mean values following the treatments. Treatment will be included as a fixed effect. 
Subject will be included as a random effect. 
 
9.0 
Confidentiality, Privacy and Data Management 
 
 
9.1 
Confidentiality 
 
9.1.1 
Identifiers associated with data and/or specimens 
 
The study data and/or specimens will not contain identifiable information. Names, addresses, 
telephone numbers, email addresses, date of birth, and visit dates will be linked to data and 
specimens via a code break list. Once enrolled in the study, all data collection will be performed 
under an assigned study ID# that is known only to the principal investigators, study 
coordinators and CRC staff (for purposes of blood collection and safety). These are the only 
persons able to connect the participant's identifiable information. 
 
9.1.1.1 Use of Codes, Master List 
If identifiers will be associated with the data and/or specimens (as indicated in 
section 9.1.1 above), describe whether a master record or list containing a code 
(i.e., code number, pseudonyms) will be used to separate the data collected from 
identifiable information, where that master code list will be stored, who will have 
access to the master code list, and when it will be destroyed. 
If identifiers are included or associated with the data as described in section 
9.1.1 above, but no master record or list containing a code will be used, it will be 
assumed by the IRB that the investigator plans to directly link the identifiers 
with the data. 
 
A master list containing a study ID number and participant’s identity will be 
used. This will be stored on a central, password protected computer file or in 
locked study files located in locked research offices of the principal 

Page 18 of 29 (V.04/27/2017) 
 
Describe where, how and for how long the data (hardcopy (paper) and/or electronic data) 
and/or specimens will be stored. NOTE: Data can include paper files, data on the internet or 
websites, computer files, audio/video files, photographs, etc. and should be considered in the 
responses. Refer to the “Investigator Manual (HRP-103)” for information about how long 
research records must be stored following the completion of the research prior to completing 
this section. HRP-103 can be accessed by clicking the Library link in CATS IRB 
(http://irb.psu.edu). 
Please review Penn State’s Data Categorization Project for detailed information regarding the 
appropriate and allowable storage of research data collected according to Penn State Policy 
AD71. Although the IRB can impose greater confidentiality/security requirements (particularly 
for sensitive data), the IRB cannot approve storage of research data in any way or using any 
service that is not permissible by Penn State Policy AD71. 
Identify who will have access to the data and/or specimens. This information should not conflict 
with information provided in section 9.1.1.1 regarding who has access to identifiable 
information, if applicable. 
If the data and/or specimens will be transferred to and/or from outside collaborators, identify 
the collaborator to whom the data and/or specimens will be transferred and how the data 
and/or specimens will be transferred. This information should not conflict with information 
provided in section 9.1.1.1 regarding who has access to identifiable information, if applicable. 
investigators. 
 
No data containing study ID#'s (code numbers) will be stored with the master 
list. Files will be maintained in locked file drawers or in password protected files 
to ensure security. Upon completion of data collection, only the investigators 
and study coordinator will have access to the list. This list will be destroyed 3 
years after publication of the study results. 
 
9.1.2 
Storage of Data and/or Specimens 
 
Data will be stored in password protected computer files, locked file cabinets, locked offices, 
and using an identification coding system. Data will be stored for 3 years after the research has 
been published. 
 
Consent forms will be stored in a locked office in a locked filing cabinet. Consent forms will 
stored for a least 3 years after the completion of the research. 
 
9.1.3 
Access to Data and/or Specimens 
 
The principal investigators, co-investigator, study coordinators and trained study personnel 
will have access to data and specimens. 
9.1.4 
Transferring Data and/or Specimens 
 
After collection, serum and plasma are transferred to ~1 mL aliquots – these vials 
contain only the participants study ID #, sample type (serum or plasma) and time point. The 
vials are then boxed and stored in a locked -80 degree freezer until all data collection is 
complete. Fecal samples will also be stored in a locked -80 degree freezer and the vials will 
contain no identifying information. Once the study is complete the samples will be sorted and 

Page 19 of 29 (V.04/27/2017) 
 
This section must address subject privacy and NOT data confidentiality. 
Indicate how the research team is permitted to access any sources of information about the subjects. 
 
Describe the steps that will be taken to protect subjects’ privacy interests. “Privacy interest” refers to a 
person’s desire to place limits on whom they interact with or to whom they provide personal information. 
Describe what steps you will take to make the subjects feel at ease with the research situation in terms of 
the questions being asked and the procedures being performed. “At ease” does not refer to physical 
discomfort, but the sense of intrusiveness a subject might experience in response to questions, 
examinations, and procedures. 
This section is required when research involves more than Minimal Risk to subjects. As defined in “SOP: 
Definitions (HRP-001)”, available in the Library in CATS IRB (http://irb.psu.edu), Minimal Risk is defined as the 
probability and magnitude of harm or discomfort anticipated in the research that are not greater in and of 
themselves than those ordinarily encountered in daily life or during the performance of routine physical or 
psychological examinations or tests. For research involving prisoners, Minimal Risk is the probability and 
magnitude of physical or psychological harm that is normally encountered in the daily lives, or in the routine 
medical, dental, or psychological examination of healthy persons. Please complete the sections below if the 
research involves more than minimal risk to subjects OR indicate as not applicable. 
Describe the plan to periodically evaluate the data collected regarding both harms and benefits to 
determine whether subjects remain safe. 
shipped on dry ice via FedEx or a Quest Courier to the following sites for analysis: (No identifying 
information is provided with the 
samples) 
Serum/Plasma: 
- Quest diagnostics, 875 Greentree Rd., Pittsburgh, PA 
Fecal samples: 
- Wright Labs LLC, 419 14th Street, Huntingdon PA 16652 
 
9.2 
Subject Privacy 
 
Once enrolled in the study, all data collection will be performed under an assigned study ID# that is 
known only to the principal investigators, co-investigators, study coordinators and CRC staff (for purposes 
of blood collection and safety). These are the only persons able to connect the participant's identifiable 
information. In addition, all study personnel have conducted IRB training and are aware of the 
importance involved with maintaining privacy and confidentiality when interacting with participants in 
any setting. 
 
All clinical visits are conducted at the CRC by highly trained clinical staff. The CRC maintains the same 
level of privacy and sterility that is expected in a hospital setting and all clinical assessments are 
conducted within private rooms. 
 
10.0 Data and Safety Monitoring Plan 
 
 
10.1 
Periodic evaluation of data 
 
Not applicable 

Page 20 of 29 (V.04/27/2017) 
 
Describe the data that are reviewed, including safety data, untoward events, and efficacy data. 
Describe the method by which the safety information will be collected (e.g., with case report forms, at 
study visits, by telephone calls and with subjects). 
Describe the frequency of data collection, including when safety data collection starts. 
Identify the individuals who will review the data. The plan might include establishing a data and safety 
monitoring committee and a plan for reporting data monitoring committee findings to the IRB and the 
sponsor. 
Describe the frequency or periodicity of review of cumulative data. 
Describe the statistical tests for analyzing the safety data to determine whether harms are occurring. 
Describe any conditions that trigger an immediate suspension of research. 
10.2 
Data that are reviewed 
 
Not applicable 
 
10.3 
Method of collection of safety information 
 
Not applicable 
 
10.4 
Frequency of data collection 
 
Not applicable 
 
10.5 
Individuals reviewing the data 
 
Not applicable 
 
10.6 
Frequency of review of cumulative data 
 
Not applicable 
 
10.7 
Statistical tests 
 
Not applicable 
 
10.8 
Suspension of research 
 
 
11.0 Risks 
Not applicable 
 
 
 
Gastrointestinal symptoms: 
List the reasonably foreseeable risks, discomforts, hazards, or inconveniences to the subjects related the 
subjects’ participation in the research. For each potential risk, describe the probability, magnitude, duration, 
and reversibility. Consider all types of risk including physical, psychological, social, legal, and economic risks. If 
applicable, indicate which procedures may have risks to the subjects that are currently unforeseeable. If 
applicable, indicate which procedures may have risks to an embryo or fetus should the subject be or become 
pregnant. If applicable, describe risks to others who are not subjects. 
Please keep in mind that loss of confidentiality is a potential risk when conducting human subject research and 
should be addressed as such. 

Page 21 of 29 (V.04/27/2017) 
 
Describe the potential benefits that individual subjects may experience from taking part in the research. 
If there is no direct benefit to subjects, indicate as such. Compensation is not considered a benefit. 
Compensation should be addressed in section 14.0. 
Some participants may experience GI (stomach) upset from the changes to their diet with incorporation of the 
test foods; symptoms may include, but are not limited to, any of the following: constipation/diarrhea, nausea, 
and bloating. This will likely subside once the participant becomes accustomed to the study foods. 
 
Food Allergies: 
Individuals will be asked to report any food allergies during the telephone screen, however it is possible that an 
unknown food allergy may manifest during the study. This is most likely to occur within the first week of the 
treatment period. Each day participants will be asked to complete a daily monitoring form so that we may track 
any adverse events, including potential food allergies, and identify the source as soon as possible. In addition, 
we ask participants to please inform study staff immediately should any adverse events occur. 
Blood Sampling: 
Blood draws often cause mild pain, swelling or bleeding. There may be some bruising (blood under the surface 
of the skin), which can be minimized by pressing on the site after the needle is removed. There is also a slight 
chance of infection, dizziness or fainting. These risks will be minimized and most likely eliminated by having 
trained staff draw the blood in a clinical setting using sterile supplies. If dizziness or fainting occurs, the 
symptoms will be alleviated by having the participant lie flat with their feet raised. If these should occur, the 
participant may be asked to remain at the clinic until the nurses have checked the participant’s blood pressure 
and are sure the participant is ok to leave. 
 
SphygmoCor (Pulse Wave Analysis and Pulse Wave Velocity): 
There are no known risks associated with these measurements. The sensation of pressure from the blood 
pressure cuff or hand-held probe may be uncomfortable. There is a possibility for red blotching or mild bruising 
(petechiae) appearing on the skin above and below the location of the blood pressure cuff. Studies indicate that 
petechiae are rare (occurring in less than ½ of 1% of patients) and it is typically not uncomfortable and does not 
require treatment. 
 
Loss of Confidentiality: 
There is always a potential for loss of confidentiality despite our best efforts. To prevent this from occurring all 
records are coded with a unique ID number and no names are used. Records containing names or other 
identifying information are kept under lock at the PI’s research office. All records associated with an individual’s 
participation in the study will be subject to the usual confidentiality standards applicable to medical records. In 
the event of publication of this research, no personal identifying information will be disclosed. 
Fecal Sample Collection: 
Some participants may experience a certain level of embarrassment or discomfort from being asked to collect 
stool samples. 
 
12.0 Potential Benefits to Subjects and Others 
 
12.1 
Potential Benefits to Subjects 
 
Participants will receive their screening laboratory results, including a complete blood count, 
interpretation of liver and kidney function, and blood lipid values, at no cost. 

Page 22 of 29 (V.04/27/2017) 
 
Include benefits to society or others. 
Describe whether results (study results or individual subject results, such as results of investigational diagnostic 
tests, genetic tests, or incidental findings) will be shared with subjects or others (e.g., the subject’s primary care 
physicians) and if so, describe how it will be shared. 
Describe the amount and timing of any subject stipend/payment or travel reimbursement here. If there is no 
subject stipend/payment or travel reimbursement, indicate as not applicable. 
If course credit or extra credit is offered to subjects, describe the amount of credit and the available alternatives. 
Alternatives should be equal in time and effort to the amount of course or extra credit offered. 
If an existing, approved student subject pool will be used to enroll subjects, please indicate as such and indicate 
that course credit will be given and alternatives will be offered as per the approved subject pool procedures. 
12.2 
Potential Benefits to Others 
 
The findings of this study will be applicable to the 84 million adults living with pre-diabetes in the US, and 
if shown to improve glycemic control the results may be extrapolated to the 30 million adults living with 
diabetes in the U.S.[1]. This equates to approximately one third of the U.S. population, which demonstrates 
the substantial public health burden attributable to pre-diabetes and diabetes. Further demonstrating the 
critical need for strategies to improve glycemic control is data showing that 46% of adults with diabetes 
have suboptimal glycemic control[1]. This novel study will empirically test the hypothesis that nighttime 
peanut consumption improves fasting glucose levels, and thus if supported this non-pharmaceutical 
treatment strategy is likely to have substantial clinical and public health implications. The findings of this 
research will be published in peer reviewed journals and these papers will likely be cited by clinical 
management guidelines and inform dietary recommendations. Therefore, the findings of this research are 
likely to inform clinical practice and dietary guidelines for individuals with impaired fasting glucose. 
 
 
13.0 Sharing Results with Subjects 
 
 
Screening results are provided to all potential participants (regardless of their eligibility status) within 2 weeks of 
their screening appointment. All screening results are reviewed by the Nurse Practitioner or Physician at the 
Clinical Center. Should any abnormal lab values be identified that warrant further evaluation the individual will 
be contacted (by the Study Coordinator) and asked to schedule a visit with their primary care 
physician. Individual results following each treatment period may be provided to participants upon request 
following completion of all study related data collection and analyses. 
 
14.0 Subject Stipend (Compensation) and/or Travel Reimbursements 
 
 
For their time and participation in the study participants will receive monetary compensation of $400, prorated 
as follows and paid at the completion of their participation in the study: 
Completion of first treatment period = $100 
Completion of second treatment period = $300 
The total of $400 will be paid at the completion of the participant’s involvement with the study. 
Participants may not be eligible for compensation if determined that specific work or visa laws conflict. 

Page 23 of 29 (V.04/27/2017) 
 
Describe any costs that subjects may be responsible for because of participation in the research. 
If the research involves more than Minimal Risk to subjects, describe the available compensation in 
the event of research related injury. 
 
If there is no sponsor agreement that addresses compensation for medical care for research subjects 
with a research-related injury, include the following text as written - DO NOT ALTER OR DELETE: 
It is the policy of the institution to provide neither financial compensation nor free medical treatment 
for research-related injury. In the event of injury resulting from this research, medical treatment is 
available but will be provided at the usual charge. Costs for the treatment of research-related injuries 
will be charged to subjects or their insurance carriers. 
For sponsored research studies with a research agreement with the sponsor that addresses 
compensation for medical care for research-related injuries, include the following text as written - DO 
NOT ALTER OR DELETE: 
It is the policy of the institution to provide neither financial compensation nor free medical treatment 
for research-related injury. In the event of injury resulting from this research, medical treatment is 
available but will be provided at the usual charge. Such charges may be paid by the study sponsor as 
outlined in the research agreement and explained in the consent form. 
Identify and describe the facilities, sites and locations where recruitment and study procedures will be 
performed. 
 
If research will be conducted outside the United States, describe site-specific regulations or customs 
affecting the research, and describe the process for obtaining local ethical review. Also, describe the 
principal investigator’s experience conducting research at these locations and familiarity with local 
culture. 
15.0 Economic Burden to Subjects 
 
15.1 
Costs 
 
The participants will not bear any costs due to their participation in the study. 
 
15.2 
Compensation for research-related injury 
 
Not applicable – the research does not involve more than minimal risk. 
 
 
16.0 Resources Available 
 
16.1 
Facilities and locations 
 
Penn State University Clinical Research Center -The clinical aspects of this study will be conducted at the 
Clinical Research Centre (CRC) on the University Park campus of the Pennsylvania State University. The 
CRC is a purpose-built research unit that supports human clinical research trials, and is fully equipped 
with exam rooms, invasive and general procedure rooms and five hospital-style bedrooms with 
bathrooms. There is also a specimen processing room with refrigerated and unrefrigerated centrifuges 
for preparation of samples. The study investigators will work closely with experienced CRC staff 
(physicians, nurse practitioners, registered nurses and research technologists) to optimize and facilitate 
the research protocol. The principal investigators, co-investigator, and project coordinators are 
experienced with conducting research at this location and have conducted multiple clinical trials at this 
location previously. 

Page 24 of 29 (V.04/27/2017) 
 
Indicate the number of potential subjects to which the study team has access. Indicate the percentage 
of those potential subjects needed for recruitment. 
Describe how the PI will ensure that a sufficient amount of time will be devoted to conducting and 
completing the research. Please consider outside responsibilities as well as other on-going research for 
which the PI is responsible. 
Describe the availability of medical or psychological resources that subject might need as a result of 
their participation in the study, if applicable. 
Describe the training plans to ensure members of the research team are informed about the protocol 
and their duties, if applicable. 
The Penn State Metabolic Diet Study Center is a state-of-the-art facility consisting of a spacious dining 
area, a pantry and a fully-equipped kitchen specifically designed for nutrition studies. In addition, this 
area is available for small group meetings with study participants and counseling/information exchange 
with small groups of individuals. 
 
16.2 
Feasibility of recruiting the required number of subjects 
 
Given the wide age range and broad recruitment criteria we believe these methods, which have been 
successful in the past, will enable us to recruit the necessary participants within the appropriate time 
frame. 
 
16.3 
PI Time devoted to conducting the research 
 
The Principal Investigators will be responsible for assuring through personal contact between the 
coinvestigator, clinical staff and coordinators that each individual clearly understands and accepts the 
obligations incurred in the undertaking of this clinical trial. 
The Principal Investigators will ensure that the clinical staff fully understand the nature of the protocol 
and the requirements for an adequate and well-controlled study; the obligation to conduct the clinical 
investigation in accordance with the applicable federal regulations; the obligation to obtain informed 
consent in accordance with 21 CFR Part 50; the obligation to obtain IRB review and approval of a clinical 
investigation before the investigation may be initiated and to ensure continuing review of the study by 
the IRB in accordance with 21 CFR Part 56. 
16.4 
Availability of medical or psychological resources 
 
A clinician is always present during clinical testing. Highly trained nursing staff will perform 
clinical assessments. Should an individual require psychological services they will be referred to the on 
campus clinic: Psychological Clinic, 314 Moore Bldg., University Park, Phone: 865-2191. 
 
16.5 
Process for informing Study Team 
 
All study staff will be required to complete the Human Participant Training and Bloodborne Pathogen 
Training as mandated by the Pennsylvania State University Office of Research Protections. In addition, 
as part of the initial training for this study, all staff members (e.g. project managers, research 
coordinators, assistants, and Clinical Research Center [CRC] nursing staff) will conduct an initial project 
start-up meeting to review the scientific protocol and ensure all study procedures are in place. 

Page 25 of 29 (V.04/27/2017) 
 
Describe any approvals that will be obtained prior to commencing the research (e.g., from cooperating 
institutions, community leaders, schools, external sites, funding agencies). 
17.0 Other Approvals 
17.1 
Other Approvals from External Entities 
 
 
IBC approval will be obtained for the collection and analysis of blood and fecal samples. 
17.2 
Internal PSU Committee Approvals 
Check all that apply: 
Anatomic Pathology – Hershey only – Research involves the collection of tissues or use of pathologic 
specimens. Upload a copy of HRP-902 - Human Tissue For Research Form on the “Supporting 
Documents” page in CATS IRB. This form is available in the CATS IRB Library. 
Animal Care and Use – All campuses – Human research involves animals and humans or the use of 
human tissues in animals 
X Biosafety – All campuses – Research involves biohazardous materials (human biological specimens in 
a PSU research lab, biological toxins, carcinogens, infectious agents, recombinant viruses or DNA or 
gene therapy). 
 
Clinical Laboratories – Hershey only – Collection, processing and/or storage of extra tubes of body 
fluid specimens for research purposes by the Clinical Laboratories; and/or use of body fluids that 
had been collected for clinical purposes, but are no longer needed for clinical use. Upload a copy of 
HRP-901 - Human Body Fluids for Research Form on the “Supporting Documents” page in CATS IRB. 
This form is available in the CATS IRB Library. 
 
X Clinical Research Center (CRC) Advisory Committee – All campuses – Research involves the use of CRC 
services in any way. 
 
Conflict of Interest Review – All campuses – Research has one or more of study team members 
indicated as having a financial interest. 
 
Radiation Safety – Hershey only – Research involves research-related radiation procedures. All 
research involving radiation procedures (standard of care and/or research-related) must upload a 
copy of HRP-903 - Radiation Review Form on the “Supporting Documents” page in CATS IRB. This 
form is available in the CATS IRB Library. 
IND/IDE Audit – All campuses – Research in which the PSU researcher holds the IND or IDE or 
intends to hold the IND or IDE. 
 
Scientific Review – Hershey only – All investigator-written research studies requiring review by the 
convened IRB must provide documentation of scientific review with the IRB submission. The 
scientific review requirement may be fulfilled by one of the following: (1) external peer-review 
process; (2) department/institute scientific review committee; or (3) scientific review by the Clinical 
Research Center Advisory committee. NOTE: Review by the Penn State Hershey Cancer Institute 
Scientific Review Committee is required if the study involves cancer prevention studies or cancer 
patients, records and/or tissues. For more information about this requirement see the IRB website 
at: http://www.pennstatehershey.org/web/irb/home/resources/investigator 

Page 26 of 29 (V.04/27/2017) 
 
If this is a multi-site study (i.e., the study will be conducted at other institutions each with its own principal 
investigator) and you are the lead investigator, describe the processes to ensure communication among sites in 
the sections below. 
Describe the plan for regular communication between the overall study director and the other sites to 
ensure that all sites have the most current version of the protocol, consent document, etc. Describe the 
process to ensure all modifications have been communicated to sites. Describe the process to ensure 
that all required approvals have been obtained at each site (including approval by the site’s IRB of 
record). Describe the process for communication of problems with the research, interim results and 
closure of the study. 
Describe the process and schedule for data submission and provide the data security plan for data 
collected from other sites. Describe the process to ensure all engaged participating sites will safeguard 
data as required by local information security policies. 
Describe the procedures for coordination of subject enrollment and randomization for the overall 
project. 
Describe how adverse events and other information will be reported from the clinical sites to the overall 
study director. Provide the timeframe for this reporting. 
Describe the process to ensure all local site investigators conduct the study appropriately. Describe any 
on-site auditing and monitoring plans for the study. 
By submitting this study for review, you agree to the following statement – DO NOT ALTER OR DELETE: 
18.0 Multi-Site Research 
 
 
18.1 
Communication Plans 
 
Not applicable 
 
18.2 
Data Submission and Security Plan 
 
Not applicable 
 
18.3 
Subject Enrollment 
 
Not applicable 
 
18.4 
Reporting of Adverse Events and New Information 
 
Not applicable 
 
18.5 
Audit and Monitoring Plans 
 
Not applicable 
19.0 Adverse Event Reporting 
 
19.1 
Reporting Adverse Reactions and Unanticipated Problems to the Responsible IRB 
 
In accordance with applicable policies of The Pennsylvania State University Institutional Review Board 
(IRB), the investigator will report, to the IRB, any observed or reported harm (adverse event) 
experienced by a subject or other individual, which in the opinion of the investigator is determined to be 
(1) unexpected; and (2) probably related to the research procedures. Harms (adverse events) will be 
submitted to the IRB in accordance with the IRB policies and procedures. 

Page 27 of 29 (V.04/27/2017) 
 
By submitting this study for review, you agree to the following statement – DO NOT ALTER OR DELETE: 
If this study is collecting identifiable data and/or specimens that will be banked for future undetermined 
research, please describe this process in the sections below. This information should not conflict with 
information provided in section 9.1.1 regarding whether or not data and/or specimens will be associated with 
identifiers (directly or indirectly). 
Identify what data and/or specimens will be stored and the data associated with each specimen. 
Identify the location where the data and/or specimens will be stored. 
Identify how long the data and/or specimens will be stored. 
Identify who will have access to the data and/or specimens. 
Describe the procedures to release the data and/or specimens, including: the process to request a 
release, approvals required for release, who can obtain data and/or specimens, and the data to be 
provided with the specimens. 
20.0 Study Monitoring, Auditing and Inspecting 
 
20.1 
Auditing and Inspecting 
 
The investigator will permit study-related monitoring, audits, and inspections by the Penn State quality 
assurance program office(s), IRB, the sponsor, and government regulatory bodies, of all study related 
documents (e.g., source documents, regulatory documents, data collection instruments, study data 
etc.). The investigator will ensure the capability for inspections of applicable study-related facilities 
(e.g., pharmacy, diagnostic laboratory, etc.). 
 
21.0 Future Undetermined Research: Data and Specimen Banking 
 
 
21.1 
Data and/or specimens being stored 
 
Blood (serum/plasma) may be stored for future testing. 
Fecal Samples: Analysis of microbial composition and identification of metabolites 
 
21.2 
Location of storage 
 
Chandlee Lab: Room 318 in a locked -80 degree freezer 
 
21.3 
Duration of storage 
 
Specimens will be destroyed 3 years after publication of results, unless permission has been granted to 
keep. If permission to keep the samples has been granted, the samples may be stored indefinitely or 
until the integrity of the sample is comprised. 
 
21.4 
Access to data and/or specimens 
 
Specimens will be boxed, labeled by sample type, study name, and dates of collection, and stored in a 
locked -80 degree freezer. Samples will only be accessible to designated staff and students for purposes 
outlined in this proposal. 
 
21.5 
Procedures to release data or specimens 

Page 28 of 29 (V.04/27/2017) 
 
Describe the process for returning results about the use of the data and/or specimens. 
List relevant references in the literature which highlight methods, controversies, and study outcomes. 
All specimens will be coded with non-identifiable labels. Participants may elect to make their samples 
available for additional analyses by study collaborators. 
21.6 
Process for returning results 
 
No specimens are returned to participants. 
 
22.0 References 
 
 
 
1. 
National Center for Chronic Disease Prevention and Health Promotion. National Diabetes Statistics 
Report, 2017: Estimates of Diabetes and Its Burden in the United States; 2017. 
2. 
Unwin N, Shaw J, Zimmet P, Alberti K. Impaired glucose tolerance and impaired fasting glycaemia: the 
current status on definition and intervention. Diabetic medicine 2002; 19: 708-723 doi: 
3. 
Ligthart S, van Herpt TTW, Leening MJG, Kavousi M, Hofman A, Stricker BHC, van Hoek M, et al. 
Lifetime risk of developing impaired glucose metabolism and eventual progression from prediabetes to type 2 
diabetes: a prospective cohort study. The Lancet Diabetes & Endocrinology 2016; 4: 44-51 doi: 
http://dx.doi.org/10.1016/S2213-8587(15)00362-9] 
4. 
Liu T. A Comparison of Biological and Physical Risk Factors for Cardiovascular Disease in 
Overweight/Obese Individuals With and Without Prediabetes. Clinical Nursing Research 2016; doi: 
10.1177/1054773816658644] 
5. 
The Emerging Risk Factors Collaboration. Diabetes mellitus, fasting blood glucose concentration, and 
risk of vascular disease: A collaborative meta-analysis of 102 prospective studies. The Lancet 2010; 375: 2215- 
2222 doi: http://dx.doi.org/10.1016/S0140-6736(10)60484-9] 
6. 
Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, et al. Diabetes 
mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 
prospective studies. Lancet (London, England) 2010; 375: 2215-22 [PMC2904878 doi: 10.1016/s0140- 
6736(10)60484-9] 
7. 
Aune D, Keum N, Giovannucci E, Fadnes L, Boffetta P, Greenwood D, Tonstad S, et al. Nut 
consumption and risk of cardiovascular disease, total cancer, all-cause and cause-specific mortality: a 
systematic review and dose-response meta-analysis of prospective studies. BMC Medicine 2016; 14: 207 doi: 
8. 
Luo C, Zhang Y, Ding Y, Shan Z, Chen S, Yu M, Hu FB, et al. Nut consumption and risk of type 2 
diabetes, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis. Am J Clin Nutr 
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9. 
Dyer-Parziale M. The effect of extend bar containing uncooked cornstarch on night-time glycemic 
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10. 
Monnier L, Colette C, Dejager S, Owens D. Magnitude of the Dawn Phenomenon and Its Impact on the 
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11. 
Porcellati F, Lucidi P, Bolli GB, Fanelli CG. Thirty Years of Research on the Dawn Phenomenon: 
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Stephenson JM, Schernthaner G. Dawn Phenomenon and Somogyi Effect in IDDM. Diabetes Care 
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Matthan NR, Ausman LM, Meng H, Tighiouart H, Lichtenstein AH. Estimating the reliability of 
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16. 
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Liu Z, Lin X, Huang G, Zhang W, Rao P, Ni L. Prebiotic effects of almonds and almond skins on 
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