The Acute Effect of Propionate on Energy Homeostasis
Phase: NA
Conditions: Obesity
Sponsor: Imperial College London

REC Reference number: 230710                 Version 1 (14/10/17)                  Imperial College London 
 
 
 
 
 
 
 
 
 
 
 
 
 
PROTOCOL 
 
 
 
 
 
The Acute Effect of Propionate on Energy 
Homeostasis 
 
 
 
 
 
Propionate and Energy Homeostasis 
 
 
 
 
 
 
 
 
 
 
 
 
 

REC Reference number: 230710                 Version 1 (14/10/17)                  Imperial College London 
 
 
Main Sponsor   
 
Imperial College London 
 
 
 
 
 
 
Protocol authorised by 
 
 
 
 
 
 
 
Professor Gary Frost 
Professor of Nutrition and Dietetics, 
Department of Investigative Medicine, 
Hammersmith Hospital Campus, Imperial College, 
6th Floor, Commonwealth Building, 
Du Cane Road, London, 
W12 0NN 
 
 
Dr. Edward Chambers 
Research Associate 
Department of Investigative Medicine, 
Hammersmith Hospital Campus, Imperial College, 
6th Floor, Commonwealth Building, 
Du Cane Road, London, 
W12 0NN 
 
 
 
Alia Sukkar RD 
PhD Candidate  
Department of Investigative Medicine, 
Hammersmith Hospital Campus, Imperial College, 
6th Floor, Commonwealth Building, 
Du Cane Road, London, 
W12 0NN 
 
 

REC Reference number: 230710                 Version 1 (14/10/17)                  Imperial College London 
 
 
Long title: 
The Acute Effect of Propionate on Energy Homeostasis 
Short title: 
Propionate and Energy Homeostasis 
 
Study Management Group 
 
Chief Investigator 
Professor Gary Frost 
 
Co-investigators 
Dr. Edward Chambers 
 
Statistician 
Dr. Douglas Morrison 
 
Study Management 
Dr Edward Chambers 
 
 
 
Sponsor 
 
Imperial College is the main research sponsor for this study. For further information regarding the sponsorship 
conditions, please contact the Research Governance Manager at: 
 
Joint Research Compliance Office 
Imperial College London and Imperial College Healthcare NHS Trust 
Room 215, Level 2 
Medical School Building  
 Norfolk Place  
 London, W2 1PG 
 
www.imperial.ac.uk/clinicalresearchoffice 
 
 
 
 
 
PROBLEMS RELATED TO THIS TRIAL SHOULD BE REFERRED TO PROFESSOR GARY FROST 
g.frost@imperial.ac.uk 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

REC Reference number: 230710                 Version 1 (14/10/17)                  Imperial College London 
 
 
 
Table of Contents 
1. 
INTRODUCTION ......................................................................................................... 5 
2. 
Study 1: The acute effects of propionate on energy metabolism during fasting. ......... 7 
3. 
Study 2: The acute effects of propionate on energy metabolism during exercise. ....... 9 
4. 
Study 3: The acute effects of propionate on postprandial metabolism: .................... 11 
5. 
PARTICIPANT ENTRY ............................................................................................... 13 
INCLUSION CRITERIA ...................................................................................................... 13 
EXCLUSION CRITERIA ...................................................................................................... 13 
WITHDRAWAL CRITERIA ................................................................................................. 14 
5. ADVERSE EVENTS ........................................................................................................ 14 
6. REGULATORY ISSUES .................................................................................................. 15 
7. PUBLICATION POLICY .................................................................................................. 16 
8. References:................................................................................................................. 16 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

REC Reference number: 230710                 Version 1 (14/10/17)                  Imperial College London 
 
 
 
1. INTRODUCTION 
 
Dietary fibres have long been recognized for their important role in a healthy diet due to their 
negative association with, and even management of, chronic diseases such as obesity, diabetes, 
metabolic syndrome, cardiovascular disease and inflammatory-bowel disease among others (1–
3).Emerging evidence has suggested that these benefits could largely be attributed to short chain 
fatty acids (SCFA) (acetate, propionate and butyrate), the main by-products of fibre fermentation in 
the gut (1,4). Our research group has demonstrated that a long-term elevation in the SCFA 
propionate significantly reduced body weight gain in overweight adults and reduced liver fat storage 
(5). 
 
The current project will examine potential mechanisms for the positive effect of propionate on 
energy homeostasis and metabolic profile. We will examine the effects of propionate on circulating 
glucose, insulin and lipid levels at rest, following moderate-intensity exercise and mixed meal 
tolerance test.  
 
To acutely increase propionate absorption from the gut the present project will use a simple 
nutritional supplement: sodium propionate in a hydroxypropylmethyl cellulose (HPMC) capsule. This 
capsule is coated with an enteric film which prevents gastric digestion until the capsule reaches the 
intestine. This nutritional supplement has been used in human volunteers in a previously approved 
ethics application (12/LO/1769: Oral propionate and glucose homeostasis). A 5g acute dose of 
sodium propionate had previously been tested and reported no adverse effects (6) . The MHRA have 
confirmed that encapsulated sodium propionate is not classed as an investigative medicinal product 
(correspondence attached with application).       
 
 
STUDY: The acute effects of short chain fatty acids on energy homeostasis 
 
Obesity is a major global health concern where it has more than doubled since 1980 inflicting around 
13% of the population world-wide(7). In England alone, more than half of the population is either 
overweight or obese (8). Causes of obesity are mainly environmental where excess dietary intake 
and physical inactivity play a major role (9). Obesity increases the risk of various chronic diseases 
such as type 2 diabetes, hypertension, dyslipidaemia and cardiovascular disease which place a 
significant economic burden on health care systems (9,10). And these diseases often develop as a 
consequence of the metabolic changes that occur with obesity such as disturbances in glucose 
homeostasis, insulin sensitivity and lipid profile (11,12). Thus, efforts have been directed to address 
these metabolic abnormalities and environmental causes to help alleviate obesity and its adverse 
outcomes.  
Short chain fatty acids, acetate, propionate and butyrate, have shown to exert multiple physiological 
changes that are beneficial in obese states. Propionate, in particular, has shown to exert multiple 
physiological benefits. For instance, it seems to regulate hepatic lipid metabolism through a 
reduction in intrahepatic triglyceride concentration (5). It can also enhance the lipid buffering 
capacity of adipose tissue through an increase in lipoprotein lipase activity and consequently, can 
decrease serum free fatty acids (13). Moreover, it can increase energy expenditure via diet-induced- 
thermogenesis through activation of the sympathetic nervous system (14), and can reduce energy 
intake through its effect on appetite hormones and decrease long-term weight gain and fat 
accretion in overweight adults (5). As for glucose metabolism, propionate serves as a gluconeogenic 

REC Reference number: 230710                 Version 1 (14/10/17)                  Imperial College London 
 
 
substrate (15–17) and can thus spare/preserve the use of amino acids for gluconeogenesis (18,19). 
Moreover, it seems to hold promising results in enhancing hepatic and peripheral insulin 
sensitivity(20) and overall glucose homeostasis (20,21).  
 
An intervention which elevates propionate release from the gut may therefore protect against 
obesity and its associated metabolic disruptions through enhanced glucose tolerance, lipid profile, 
and increased energy expenditure. Thus, the aim of this project is to investigate the acute effects of 
gut-derived propionate on the regulation of energy expenditure, substrate oxidation and overall 
metabolic profile in humans throughout different physiological states (fasting, postprandial and 
during physical activity). This study is an extrapolation based on a previously ethically approved 
research study (15/WA/0415) which demonstrated an increase in energy expenditure, lipid 
oxidation rates and circulating levels of propionate following an acute dose of 5 g sodium propionate 
supplemented over a 180 min time period. As can be seen from the below graphs, circulating levels 
of propionate increased over time to reach a peak at 180 min and thus for this study we would want 
to determine the trend in propionate levels over a longer period (300 minutes) while also examining 
energy expenditure and lipid oxidation with a properly matched energy control.  
 
 
Figure 1. The effect of oral propionate supplementation on short chain fatty acid levels in 
peripheral blood. A. Propionate (Time×Trial: P= 0.043) and B. propionate iAUC (P=0.021).  

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Figure 2. The effect of oral propionate supplementation on resting energy expenditure and 
substrate oxidation. A. Resting energy expenditure (Time×Trial: P= 0.388) and B. resting energy 
expenditure iAUC (P=0.036). C. Lipid oxidation (Time×Trial: P= 0.075) and D. lipid oxidation iAUC 
(P=0.019). 
 
2. Study 1: The acute effects of propionate on energy metabolism 
during fasting. 
 
Study methodology: A randomized, placebo controlled, double blind, cross-over study. 
 
Participants:  40 healthy male and female volunteers aged between 18 and 65 years with body mass 
index (BMI) of 18-35 kg/m2.  
 
Support of number of volunteers: A power calculation confirmed that 34 participants would be 
sufficient to detect a 5% difference in the primary outcome, resting energy expenditure, with a 
standard deviation (SD) of 10 %(α=0.05, power=0.80). 40 participants were recruited to allow a 
dropout rate of 15%. 
 

REC Reference number: 230710                 Version 1 (14/10/17)                  Imperial College London 
 
 
 
Recruitment 
 
Volunteers will be recruited via email using a healthy volunteer database of the NIHR/Wellcome 
Trust Imperial Clinical Research Facility (CRF) or via a study advertisement. Interested volunteers will 
be asked to fill in a pre-screening questionnaire and if deemed eligible will be invited for a screening 
visit at the CRF in Hammersmith Hospital.  
 
 
Visit 1- Health Screening 
 
Participants will attend the NIHR/Wellcome Trust Imperial Clinical Research Facility at Hammersmith 
Hospital where their eligibility will be assessed via an interview which discusses medical history, 
family history of medical illness and drug history. They will have a blood test (Full blood count liver 
function test, urea & electrolytes and lipids) and height and weight measurements will also be taken. 
They will also have an electrocardiogram (ECG) and blood pressure will be recorded. All women of 
child bearing age will have a pregnancy test. These results will be examined and approved by a 
qualified research doctor before the volunteers will be formally enrolled in the study. 
 
 
Visits 2,3,4– Study Visits 
 
Subjects will be asked to complete three study visits that will last approximately 6 hours each. The 
three study visits will need to be separated by a period of at least 3 days. Participants will be told not 
to start any other new diets or intensive exercise regimes during the study period as this may give us 
conflicting results.  
 
In a randomized order, volunteers will complete the following three study visits: 
1. Sodium Chloride (Sodium Control)  
2. Palmitic Acid (Fatty Acid Control) 
3. Sodium Propionate  
 
The day prior to each study visit, participants will be requested to refrain from strenuous exercise, 
caffeine and alcohol. Participants will then be requested to fast overnight (they are allowed to drink 
water) and will come to the NIHR/Wellcome Trust Imperial Clinical Research Facility at 
Hammersmith Hospital the following morning. Fasting blood samples will be taken through an 
intravenous peripheral cannula at -15 and 0 min.   
 
Between the fasting blood samples, resting energy expenditure will be measured with a standard 
indirect calorimeter.  The calorimeter captures expired air from a large, transparent canopy, worn 
over the head and thorax, and is typically very well tolerated.  Each participant will be asked to lie in 
a semi-recumbent position under the canopy.  Measurements will be taken for 20 min in order to 
assess the participants’ resting metabolic rate (RMR) and respiratory quotient (RQ). Additional 
measures of RMR and RQ will be recorded at 40-60 min, 100-120 min,-160-180 220-240 min and 
280-300. 
 
Following the 0 min sample volunteers will ingest a capsule containing either 1g sodium propionate 
(Propionate) or 1 g sodium chloride (Sodium Control) or 1g palmitic acid (fatty acid control) at 30, 
60, 90 and 120 (5g in total) 
 

REC Reference number: 230710                 Version 1 (14/10/17)                  Imperial College London 
 
 
Blood samples will be taken at 30, 60, 90, 120, 150, 180, 210, 240 and 300 min to measure 
hormones and metabolites. 110 ml (11 × 10 ml) will be collected throughout each study visit. Blood 
pressure and heart rate will be measured at baseline and every hour at 60,120,180,240 and 300 min. 
Urine will be collected throughout the study visit to measure urea concentrations for calculation of 
protein oxidation rates. Subjects will empty their bladder before baseline blood samples and collect 
all urine thereafter for a period of 300 min using appropriate measurement containers. 
 
Figure 1: Study visit protocol for study 1. 
 
 
3. Study 2: The acute effects of propionate on energy metabolism 
during exercise. 
 
Study methodology: A randomized, placebo controlled, double blind, cross-over study. 
 
Participants:  40 healthy male and female volunteers aged between 18 and 65 years with body mass 
index (BMI) of 18-35 kg/m2.  
 
Support of number of volunteers: A power calculation confirmed that 34 participants would be 
sufficient to detect a 5% difference in the primary outcome, resting energy expenditure, with a 
standard deviation (SD) of 10 %(α=0.05, power=0.80). 40 participants were recruited to allow a 
dropout rate of 15%. 
 
Recruitment 
 
Volunteers will be recruited via email using a healthy volunteer database of the NIHR/Wellcome 
Trust Imperial Clinical Research Facility (CRF) or via a study advertisement. Interested volunteers will 
be asked to fill in a pre-screening questionnaire and if deemed eligible will be invited for a screening 
visit at the CRF in Hammersmith Hospital.  
 
 
Visit 1- Health Screening 
 

REC Reference number: 230710                 Version 1 (14/10/17)                  Imperial College London 
 
 
Participants will attend the NIHR/Wellcome Trust Imperial Clinical Research Facility at Hammersmith 
Hospital where their eligibility will be assessed via an interview which discusses medical history, 
family history of medical illness and drug history. They will have a blood test (Full blood count liver 
function test, urea & electrolytes and lipids) and height and weight measurements will also be taken. 
They will also have an electrocardiogram (ECG) and blood pressure will be recorded. All women of 
child bearing age will have a pregnancy test. These results will be examined and approved by a 
qualified research doctor before the volunteers will be formally enrolled in the study. 
 
Visit 2 – Maximal Exercise Test 
 
Subjects will come to the NIHR/Wellcome Trust Imperial Clinical Research Facility at Hammersmith 
Hospital and perform an incremental exercise test to volitional exhaustion on a cycle ergometer.  
Volunteers will start cycling at 50 Watts (W) and the workload will increase in 25 W increments 
every 3 min until voluntary exhaustion. This will determine maximal oxygen uptake (VO2max), 
maximal aerobic power output (Wmax) and maximal heart rate (HRmax). Non-invasive measures of 
respiratory exchange and heart rate will be recorded throughout the test. The maximal exercise test 
is a common measurement in exercise physiology research and presents no greater risk than the 
exercise activities normally undertaken by the recruited volunteers.  The visit would last 
approximately 1 hour. 
 
Visits 3,4,5 – Study Visits 
 
Subjects will be asked to complete three study visits that will last approximately 6 hours each. The 
three study visits will need to be separated by a period of at least 3 days. Participants will be told not 
to start any other new diets or intensive exercise regimes during the study period as this may give us 
conflicting results.  
 
In a randomized order, volunteers will complete the following three study visits: 
1. Sodium Chloride (Sodium Control)  
2. Palmitic Acid (Fatty Acid Control) 
3. Sodium Propionate  
 
The day prior to each study visit, participants will be requested to refrain from strenuous exercise, 
caffeine and alcohol. Participants will then be requested to fast overnight (they are allowed to drink 
water) and will come to the NIHR/Wellcome Trust Imperial Clinical Research Facility at 
Hammersmith Hospital the following morning. Fasting blood samples will be taken through an 
intravenous peripheral cannula at -15 and 0 min.   
 
Between the fasting blood samples, resting energy expenditure will be measured with a standard 
indirect calorimeter.  The calorimeter captures expired air from a large, transparent canopy, worn 
over the head and thorax, and is typically very well tolerated.  Each participant will be asked to lie in 
a semi-recumbent position under the canopy.  Measurements will be taken for 20 min in order to 
assess the participants’ resting metabolic rate (RMR) and respiratory quotient (RQ). Additional 
measures of RMR and RQ will be recorded at 40-60 min, 100-120 min,-160-180 220-240 min and 
280-300. 
 
Following the 0 min sample volunteers will ingest a capsule containing either 1g sodium propionate 
(Propionate) or 1 g sodium chloride (Sodium Control) or 1g palmitic acid (fatty acid control) at 30, 
60, 90 and 120 (5g in total) 
 

REC Reference number: 230710                 Version 1 (14/10/17)                  Imperial College London 
 
 
At 180 min, volunteers will have their heart rate recorded while they complete 60 min of constant-
load cycling at a workload corresponding to 40% Wmax, determined from Visit 2 whilst breathing 
through a mouthpiece connected to an indirect calorimeter to determine energy expenditure and 
substrate oxidation rates during exercise. Blood samples will be taken at 30, 60, 90, 120, 150, 180, 
210, 240 and 300 min to measure hormones and metabolites. 110 ml (11 × 10 ml) will be collected 
throughout each study visit. Blood pressure and heart rate will be measured at baseline and every 
hour at 60,120,180,240 and 300 min. Urine will be collected throughout the study visit to measure 
urea concentrations for calculation of protein oxidation rates. Subjects will empty their bladder 
before baseline blood samples and collect all urine thereafter for a period of 300 min using 
appropriate measurement containers. 
 
Figure 2: Study visit protocol for study 2. 
 
 
4. Study 3: The acute effects of propionate on postprandial 
metabolism: 
 
Study methodology: A randomized, placebo controlled, double blind, cross-over study. 
 
Participants:  40 healthy male and female volunteers aged between 18 and 65 years with body mass 
index (BMI) of 18-35 kg/m2.  
 
Support of number of volunteers: A power calculation confirmed that 34 participants would be 
sufficient to detect a 5% difference in the primary outcome, resting energy expenditure, with a 
standard deviation (SD) of 10 %(α=0.05, power=0.80). 40 participants were recruited to allow a 
dropout rate of 15%.. 
 
Recruitment 
 
Volunteers will be recruited via email using a healthy volunteer database of the NIHR/Wellcome 
Trust Imperial Clinical Research Facility (CRF) or via a study advertisement. Interested volunteers will 
be asked to fill in a pre-screening questionnaire and if deemed eligible will be invited for a screening 
visit at the CRF in Hammersmith Hospital.  

REC Reference number: 230710                 Version 1 (14/10/17)                  Imperial College London 
 
 
 
 
Visit 1- Health Screening 
 
Participants will attend the NIHR/Wellcome Trust Imperial Clinical Research Facility at Hammersmith 
Hospital where their eligibility will be assessed via an interview which discusses medical history, 
family history of medical illness and drug history. They will have a blood test (Full blood count liver 
function test, urea & electrolytes and lipids) and height and weight measurements will also be taken. 
They will also have an electrocardiogram (ECG) and blood pressure will be recorded. All women of 
child bearing age will have a pregnancy test. These results will be examined and approved by a 
qualified research doctor before the volunteers will be formally enrolled in the study. 
 
Visits 2,3,4 – Study Visits 
 
Subjects will be asked to complete four study visits that will last approximately 6 hours each. The 
three study visits will need to be separated by a period of at least 3 days. Participants will be told not 
to start any other new diets or intensive exercise regimes during the study period as this may give us 
conflicting results.  
 
In a randomized order, volunteers will complete the following four study visits: 
1. Sodium Chloride (Sodium Control)  
2. Palmitic Acid (Fatty Acid Control) 
3. Sodium Propionate 
 
The day prior to each study visit, participants will be requested to refrain from strenuous exercise, 
caffeine and alcohol. Participants will then be requested to fast overnight (they are allowed to drink 
water) and will come to the NIHR/Wellcome Trust Imperial Clinical Research Facility at 
Hammersmith Hospital the following morning. Fasting blood samples will be taken through an 
intravenous peripheral cannula at -15 and 0 min.   
 
Between the fasting blood samples, resting energy expenditure will be measured with a standard 
indirect calorimeter.  The calorimeter captures expired air from a large, transparent canopy, worn 
over the head and thorax, and is typically very well tolerated.  Each participant will be asked to lie in 
a semi-recumbent position under the canopy.  Measurements will be taken for 15 min in order to 
assess the participants’ resting metabolic rate (RMR) and respiratory quotient (RQ). Additional 
measures of RMR and RQ will be recorded at 40-60 min, 100-120 min,-160-180 220-240 min and 
280-300. 
 
Following the 0 min sample volunteers will ingest a capsule containing either 1g sodium propionate 
(Propionate) or 1 g sodium chloride (Sodium Control) or 1g palmitic acid (fatty acid control) at 30, 
60, 90 and 120 (5g in total) 
 
At 180 min participants will have mixed meal tolerance test in the form of an ensure drink (500 kcal).  
Blood samples will be taken at 30, 60, 90, 120, 150, 180, 195, 210, 240 and 300 min to measure 
hormones and metabolites. 120 ml (12 × 10 ml) will be collected throughout each study visit. Blood 
pressure and heart rate will be measured at baseline and every hour at 60, 120, 180, 240 and 300 
min. 
 
Urine will be collected throughout the study visit to measure urea concentrations for calculation of 
protein oxidation rates. Subjects will empty their bladder before baseline blood samples and collect 
all urine thereafter for a period of 300 min using appropriate measurement containers. 

REC Reference number: 230710                 Version 1 (14/10/17)                  Imperial College London 
 
 
 
Figure 3: Study visit protocol for study 3. 
 
 
 
 
 
 
5. PARTICIPANT ENTRY 
 
INCLUSION CRITERIA 
 
Study 1: 
 
Healthy volunteers (body mass index (BMI) of 18-35 kg/m2) 
 
Age between 18-65 years (inclusive) 
 
Study 2: 
 
Healthy volunteers (body mass index (BMI) of 18-35 kg/m2) 
 
Age between 18-65 years (inclusive) 
Study 3: 
 
Healthy volunteers (body mass index (BMI) of 18-35 kg/m2) 
 
Age between 18-65 years (inclusive) 
 
 
EXCLUSION CRITERIA  
 
Study 1, 2, 3: 
 
Weight change of ≥ 3kg in the preceding 2 months 
 
Current smokers 

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 
Substance abuse 
 
Excess alcohol intake 
 
Pregnancy 
 
Diabetes 
 
Cardiovascular disease 
 
Cancer  
 
Gastrointestinal disease e.g. inflammatory bowel disease or irritable bowel syndrome 
 
Kidney disease 
 
Liver disease 
 
Pancreatitis 
 
Started new medication within the last 3 months likely to interfere with energy metabolism, 
appetite regulation and hormonal balance, including: anti-inflammatory drugs or steroids, 
antibiotics, androgens, phenytoin, erythromycin or thyroid hormones. 
 
Involved in current research or have recently been involved in any research prior to 
recruitment in the past 12 weeks. 
 
WITHDRAWAL CRITERIA 
 
The safety of the study participants takes priority. Any significant adverse event (as assessed by the 
researchers) will halt the study and the ethics committee and sponsor will be informed as per 
standard protocol. All adverse events will be recorded and investigators will review each adverse 
event as it arises. In addition, participants will be free to withdraw at any time and are not required 
to give a reason. 
 
 
 
 
 
 
 
 
 
5. ADVERSE EVENTS 
 
Adverse Event (AE): Any untoward medical occurrence in a patient or clinical study subject. 
 
Serious Adverse Event (SAE): Any untoward and unexpected medical occurrence that: 
 
results in death 
 
is life- threatening – refers to an event in which the subject was at risk of death at the 
time of the event; it does not refer to an event which hypothetically might have caused 
death if it was more severe. 
 
requires hospitalisation, or prolongation of existing inpatients’ hospitalisation. 
 
results in persistent or significant disability or incapacity 
 
is a congenital abnormality or birth defect 
 
Medical judgement should be exercised in deciding whether an AE is serious in other situations. 
Important AEs that are not immediately life threatening or do not result in death or hospitalisation 

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Contact details for reporting SAEs 
Fax 020 838 33142, attention Professor Gary Frost 
Please send SAE forms to Professor Gary Frost 
Tel: 020 838 33242 (Mon to Fri 09.00- 17.00) 
but may jeopardise the subject or may require intervention to prevent one of the other outcomes 
listed in the definition above, should also be considered serious. 
 
 
REPORTING PROCEDURES 
 
All adverse events should be reported. Depending on the nature of the event the reporting 
procedures below should be followed. Any questions concerning adverse event reporting should be 
directed to the Chief Investigator in the first instance. 
 
Non-serious AEs 
 
All such events, whether expected or not, should be recorded. 
 
Serious AEs (SEAs) 
 
An SAE form should be completed and faxed to the Chief Investigator within 24 h. However, relapse, 
death and hospitalisations for elective treatment of a pre-existing condition do not need reporting 
as SAEs. 
 
All SAEs should be reported to the xxxx Research Ethics Committee where in the opinion of the Chief 
Investigator the event was: 
 
‘related’, i.e. resulted from the administration of any of the research procedures; and 
 
‘unexpected’, i.e. an event that is not listed in the protocol as an expected occurrence. 
 
Reports of related and unexpected SAEs should be submitted within 15 days of the Chief Investigator 
becoming aware of the event, using the NRES SAE form. 
 
Local investigators should report any SAEs to the sponsor and their Local Research Ethics Committee 
and/ or Research and Development Office. 
 
 
 
 
 
 
 
 
 
6. REGULATORY ISSUES 
 
ETHICS APPROVAL 
This study is awaiting ethical approval from the Wales REC 6 Ethics Committee. The study will be 
conducted in accordance with the recommendations for physicians involved in research on human 
subjects adopted by the 18th World Medical Assembly, Helsinki 1964 and later revisions. 
Amendments to the protocol should be approved by the sponsor before being sent to ethics.   
 
CONSENT 
Consent to enter the study must be sought from each participant only after a full explanation has 
been given, an information leaflet offered, and time allowed for consideration. Signed participant 
consent should be obtained. The right of the participant to refuse to participate without giving 
reasons must be respected. After the participant has entered the study the clinician remains free to 

REC Reference number: 230710                 Version 1 (14/10/17)                  Imperial College London 
 
 
give alternative treatment to that specified in the protocol at any stage if he/she feels it is in the 
participant’s best interest, but the reasons for doing so should be recorded. In such cases, the 
participants remain within the study for the purposes of follow-up and data analyses. All participants 
are free to withdraw at any time from the study without giving reasons and without prejudicing 
further treatment. 
 
CONFIDENTIALITY 
The Chief Investigator will preserve the confidentiality of participants in the study and is registered 
under the Data Protection Act. 
 
DATA AND SAMPLE COLLECTION AND ANALYSIS 
All data and samples will be collected at the NIHR/Wellcome Trust Imperial Clinical Research Facility 
at Hammersmith Hospital. All data and samples will be stored and analysed at the laboratories of the 
Department of Investigative Medicine, Hammersmith Hospital. They data and samples will be 
available only to the study researchers. All analysis will be carried out on anonymised samples. The 
code linking samples to the donor will only be broken once all analysis has been conducted.  
 
INDEMNITY 
Imperial College holds negligent harm and non-negligent harm insurance policies, which apply to this 
study. 
 
SPONSOR 
Imperial College London will act as the main sponsor for this study. Delegated responsibilities will be 
assigned to the NHS trusts taking part in this study. 
 
REIMBURSMENT 
Participants will be reimbursed for their time. £75will be awarded for completion of Study 1 (£25 for 
completing Visits 2 –4). £100 will be awarded for completion of Study 2 (£25 for completing Visits 2 - 
5). £75will be awarded for completion of Study 3 (£25 for completing Visits 2 –4) 
  
AUDITS AND INSPECTIONS 
The study may be subject to inspection and audit by Imperial College London under their remit as 
sponsor and other regulatory bodies to ensure adherence to GCP and the NHS Research Governance 
Framework for Health and Social Care (2nd edition). 
 
7. PUBLICATION POLICY 
 
The findings of the research will be published in an open-access, peer-reviewed journal. In addition 
we will be collaborating with patient groups and professional groups to disseminate the findings via 
multiple media channels such as patient association publications, print and broadcast media.           
 
8. References:  
 
1.  
den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-
chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J 
Lipid Res [Internet]. 2013;54(9):2325–40. Available from: 
http://www.ncbi.nlm.nih.gov/pubmed/23821742 
2.  
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metabolic syndrome. J Nutr Biochem. 2008;19(2):71–84.  
3.  
Slavin JL. Position of the American Dietetic Association: health implications of dietary fiber. J 
Am Diet Assoc. 2008;108(10):1716–31.  
4.  
Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their 
impact on human metabolism. Gut Microbes [Internet]. 2016;7(3):189–200. Available from: 
http://dx.doi.org/10.1080/19490976.2015.1134082 
5.  
Chambers ES, Viardot A, Psichas A, Morrison DJ, Murphy KG, Zac-Varghese SE, et al. Effects of 
targeted delivery of propionate to the human colon on appetite regulation, body weight 
maintenance and adiposity in overweight adults. Gut [Internet]. 2015;64(11):1744–54. 
Available from: http://www.ncbi.nlm.nih.gov/pubmed/25500202 
6.  
Canfora EE, van der Beek CM, Jocken JWE, Goossens GH, Holst JJ, Olde Damink SWM, et al. 
Colonic infusions of short-chain fatty acid mixtures promote energy metabolism in 
overweight/obese men: a randomized crossover trial. Sci Rep [Internet]. 2017;7(1):2360. 
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WHO. Obesity and Overweight [Internet]. Fact Sheet. 2016 [cited 2017 May 22]. Available 
from: http://www.who.int/mediacentre/factsheets/fs311/en/ 
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Baker BC. Obesity Statistics. 2017;(3336).  
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Rössner S. Obesity: the disease of the twenty-first century. Int J Obes [Internet]. 
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