Clinical trial NCT04267770
Conditions: Type 1 Diabetes
Sponsor: Imperial College London
Start date: 2018-04-10; Completion date: 2018-11-09
Enrollment: 17 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Randomised controlled trial to contribute to the evidence base for the optimal initial insulin profile for adults with type 1 diabetes commencing insulin pump therapy.

Detailed description:
Initiation of insulin pump therapy in people with type 1 diabetes requires conversion of a basal insulin dose, given as once or twice daily long-acting insulin, to a continuous basal infusion regimen. This conversion may be based on basal insulin dose only, or total daily insulin dose, and may result in a flat basal insulin profile or an initial variable basal rate.

Initial variable basal rates aim to replicate circadian changes in insulin requirements and are derived from total basal insulin in adults over 24 years old, and from weight in adults aged 18 to 24 years. Initial rates were developed from 63 well-controlled people with type 1 diabetes over 14 years of age and have been assessed against a flat basal rate in a small randomised controlled trial with 12 participants. Mean glucose was lower in the circadian basal rate group with particular differences noted in the early morning when glucose rises were more pronounced in the flat basal rate group1.

In 50 people with type 1 diabetes treated with insulin pump therapy, HbA1c was lower in those with lower basal rates at midnight, and in those with higher basal rates in the afternoon, suggesting a benefit of circadian patterns2. In 33 people with type 1 diabetes over 16 years of age basal rate distribution established at commencement of pump therapy did not alter over 6 months3. However, a 6 month cross-over study of circadian rates and oligophasic basal rates showed no difference in HbA1c4.

Following initiation on insulin pump therapy basal rates are personalised to capillary blood and continuous interstitial fluid glucose monitoring.

In adults with type 1 diabetes starting insulin pump therapy there are limited data to guide the optimal insulin profile to rapidly achieve target glucose and minimise healthcare professional input.

Arms: arm 1: Initial variable basal rates aim to replicate circadian changes in insulin requirements and are derived from total basal insulin in adults over 24 years old, and from weight in adults aged 18 to 24 years. arm 2: flat basal rate
Interventions: intervention 1: Insulin (circadian) intervention 2: Insulin (flat rate)
Intervention descriptions: intervention 1: Participant's own insulin adjusted to circadian infusion rates intervention 2: Participant's own insulin set to flat basal rates

Protocol documents:
Prot_SAP_000.pdf: 
FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
 
 
FIRST1D 
 
 
 
A Study of Flat and Circadian Insulin Infusion 
Rates in Continuous Subcutaneous Insulin 
Infusion (CSII) in Adults with Type 1 Diabetes 
 
 
 
V1.7 – 23.2.18 
 
 
 
MAIN SPONSOR: Imperial College London 
FUNDERS: Roche 
STUDY COORDINATION CENTRE: Imperial College London 
NRES reference: 237129 
 
 
Protocol authorised by: 
 
Name & Role 
Date 
Signature 


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
 
Study Management Group 
 
Chief Investigator: Professor Nick Oliver 
 
Co-investigators: Miss Sian Rilstone & Dr Monika Reddy 
 
Statistician: Dr Ian Godsland 
 
Study Management: Miss Sian Rilstone 
 
 
 
 
Clinical Queries 
 
Clinical queries should be directed to Professor Nick Oliver who will direct the query to the 
appropriate person 
 
 
 
Sponsor 
Imperial College London/Imperial College Healthcare NHS Trust (delete as applicable) is the 
main research Sponsor for this study. For further information regarding the sponsorship 
conditions, please contact the Head of Regulatory Compliance at: 
 
Joint Research Compliance Office 215, Level 2 Medical School 
Norfolk Place 
 
 
London W2 1PG 
Tel: 0207 594 1872 
 
 
Funder 
Roche 
 
 
This protocol describes the FIRST1D study and provides information about procedures for 
entering participants. Every care was taken in its drafting, but corrections or amendments may 
be necessary. These will be circulated to investigators in the study. Problems relating to this 
study should be referred, in the first instance, to the Chief Investigator. 
 
This study will adhere to the principles outlined in the NHS Research Governance Framework 
for Health and Social Care (2nd edition). It will be conducted in compliance with the protocol, 
the Data Protection Act and other regulatory requirements as appropriate. 
 
 
 


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
Contents 
Study Management Group .................................................................................................... 2 
Clinical Queries ..................................................................................................................... 2 
Sponsor ................................................................................................................................ 2 
Funder .................................................................................................................................. 2 
GLOSSARY OF ABBREVIATIONS ....................................................................................... 5 
KEYWORDS ......................................................................................................................... 5 
STUDY SUMMARY .............................................................................................................. 6 
REFERENCE DIAGRAM ...................................................................................................... 6 
1. 
INTRODUCTION ........................................................................................................... 7 
1.1 BACKGROUND ............................................................................................................................... 7 
1.2 RATIONALE FOR CURRENT STUDY ................................................................................................ 7 
2. 
STUDY OBJECTIVES.................................................................................................... 7 
3. 
STUDY DESIGN ............................................................................................................ 7 
3.1 STUDY OUTCOME MEASURES ....................................................................................................... 8 
Primary outcome ............................................................................................................ 8 
Secondary outcomes ........................................................................................................................... 8 
4. 
PARTICIPANT ENTRY .................................................................................................. 8 
4.1 PRE-REGISTRATION EVALUATIONS ............................................................................................... 8 
4.2 INCLUSION CRITERIA ..................................................................................................................... 9 
4.3 EXCLUSION CRITERIA..................................................................................................................... 9 
4.4 WITHDRAWAL CRITERIA................................................................................................................ 9 
5. 
ADVERSE EVENTS ...................................................................................................... 9 
5.1 DEFINITIONS .................................................................................................................................. 9 
5.2 REPORTING PROCEDURES ........................................................................................................... 10 
5.2.1 Non serious AEs ................................................................................................. 10 
5.2.2 Serious AEs ........................................................................................................ 10 
6. 
ASSESSMENT AND FOLLOW-UP .............................................................................. 12 
7. 
STATISTICS AND DATA ANALYSIS ........................................................................... 14 
8. 
REGULATORY ISSUES .............................................................................................. 14 
8.1 ETHICS APPROVAL ....................................................................................................................... 14 
8.2 CONSENT ..................................................................................................................................... 14 
8.3 CONFIDENTIALITY........................................................................................................................ 15 
8.4 INDEMNITY .................................................................................................................................. 15 
8.5 SPONSOR ..................................................................................................................................... 15 
8.6 FUNDING ..................................................................................................................................... 15 


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
8.7 AUDITS ........................................................................................................................................ 15 
9. 
STUDY MANAGEMENT .............................................................................................. 15 
10. 
PUBLICATION POLICY ........................................................................................... 15 
11. 
REFERENCES ......................................................................................................... 15 
12. 
Appendices .............................................................................................................. 16 
Appendix 1. Summary of investigations, treatment and assessments ............................................. 17 
Appendix 2. Participant information sheet ....................................................................................... 17 
Appendix 3. Consent form ................................................................................................................ 17 
Appendix 4. GP letter ........................................................................................................................ 17 
Appendix 5. Participant invite letter ................................................................................................. 17 
Appendix 6. Questionnaire to measure awareness of hypoglycaemia (Gold) ................................. 17 
Appendix 7. Questionnaire to measure Hypoglycaemia fear (HFS-II) .............................................. 17 
Appendix 8. Questionnaire to measure general quality of life (WHOQoLBref) ................................ 17 
Appendix 9. Questionnaire to measure Diabetes distress (DDS) ..................................................... 17 
Appendix 10. Questionnaire to measure Diabetes QoL (DQOL) ....................................................... 18 
 
 
 


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
GLOSSARY OF ABBREVIATIONS 
 
 
CGM 
Continuous Glucose Monitoring 
CSII 
Continuous subcutaneous Insulin Infusion (insulin pump) 
GI 
Glycaemic Index 
HbA1c 
Haemoglobin A1 C 
MDI 
Multiple Daily Injections 
T1DM 
Type 1 Diabetes Mellitus 
 
KEYWORDS 
 
Type 1 Diabetes, Continuous subcutaneous insulin infusion (CSII), 
flat basal rate, circadian profile, continuous glucose monitoring, 
glucose, insulin, hypoglycaemia 


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
 
STUDY SUMMARY 
 
 
TITLE A Study of Flat and Circadian Insulin infusion Rates in Continuous Subcutaneous Insulin 
Infusion (CSII) in Adults with Type 1 Diabetes 
DESIGN Randomised controlled trial 
AIMS To contribute to the evidence base for the optimal initial insulin profile for adults with 
type 1 diabetes commencing insulin pump therapy. 
OUTCOME 
MEASURES 
• 
Absolute change in insulin basal rate over 24 hours after 3 rounds of basal rate 
testing (calculated by the sum of absolute changes for each 1 hour block 
compared with baseline) 
• 
Healthcare professional time spent with subject  
• 
Mean sensor glucose from continuous glucose monitoring after 3 rounds of basal
rate testing 
• 
Mean sensor glucose from continuous glucose monitoring after 1 round of basal
rate testing 
• 
Number of healthcare professional contacts 
• 
CGM outcomes 
• 
Severe hypoglycaemia 
• 
Insulin outcomes 
• 
Healthcare professional qualitative feedback 
POPULATION People with Type 1 Diabetes commencing CSII 
ELIGIBILITY Participants identified in type 1 diabetes clinics in Imperial College Healthcare NHS 
Trust 
DURATION 4 weeks plus 1 week pre-randomisation assessment 
 
 
REFERENCE DIAGRAM 
 


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
 
1. INTRODUCTION 
1.1 BACKGROUND 
 
Initiation of insulin pump therapy in people with type 1 diabetes requires conversion of a basal 
insulin dose, given as once or twice daily long-acting insulin, to a continuous basal infusion 
regimen. This conversion may be based on basal insulin dose only, or total daily insulin dose, 
and may result in a flat basal insulin profile or an initial variable basal rate.  
 
Initial variable basal rates aim to replicate circadian changes in insulin requirements and are 
derived from total basal insulin in adults over 24 years old, and from weight in adults aged 18 
to 24 years. Initial rates were developed from 63 well-controlled people with type 1 diabetes 
over 14 years of age and have been assessed against a flat basal rate in a small randomised 
controlled trial with 12 participants. Mean glucose was lower in the circadian basal rate group 
with particular differences noted in the early morning when glucose rises were more 
pronounced in the flat basal rate group1. 
 
In 50 people with type 1 diabetes treated with insulin pump therapy, HbA1c was lower in those 
with lower basal rates at midnight, and in those with higher basal rates in the afternoon, 
suggesting a benefit of circadian patterns2. In 33 people with type 1 diabetes over 16 years of 
age basal rate distribution established at commencement of pump therapy did not alter over 
6 months3. However, a 6 month cross-over study of circadian rates and oligophasic basal rates 
showed no difference in HbA1c4. 
 
Following initiation on insulin pump therapy basal rates are personalised to capillary blood and 
continuous interstitial fluid glucose monitoring. 
 
In adults with type 1 diabetes starting insulin pump therapy there are limited data to guide 
the optimal insulin profile to rapidly achieve target glucose and minimise healthcare 
professional input. 
 
 
1.2 RATIONALE FOR CURRENT STUDY 
 
 
 
Hypothesis: Circadian insulin infusion rates in CSII naïve people with type 1 diabetes are 
closer to optimal basal rates, compared with a flat initial rate 
 
 
2. STUDY OBJECTIVES 
 
Objective: To contribute to the evidence base for the optimal initial insulin profile for adults 
with type 1 diabetes commencing insulin pump therapy. 
 
 
3. STUDY DESIGN 
 
Type of study:  
Randomised controlled trial 
 
Duration: 
 
4 week trial with 1 week pre-randomisation assessment 
 


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
Number and type of subjects:  
16 participants with type 1 diabetes referred for CSII, randomised 1:1 to circadian insulin 
infusion rates or flat rates.  
 
Recruitment will be undertaken in the T1DM clinics at Imperial College Healthcare NHS Trust. 
Participant information sheets will be given to potential subjects who have been assessed and 
screened for insulin pump therapy, either in person in clinic, or via post with a participant 
invitation letter. After a minimum of 24 hours and following any questions, informed consent 
will be taken. 
 
 
 
 
3.1 STUDY OUTCOME MEASURES 
Primary outcome:   
• 
Absolute change in insulin basal rate over 24 hours after 3 rounds of basal rate testing 
(calculated by the sum of absolute changes for each 1 hour block compared with 
baseline) 
 
Secondary outcomes: 
 
• 
Healthcare professional time spent with subject  
• 
Mean sensor glucose from continuous glucose monitoring after 3 rounds of basal rate 
testing 
• 
Mean sensor glucose from continuous glucose monitoring after 1 round of basal rate 
testing 
• 
Number of healthcare professional contacts 
• 
CGM outcomes 
o %time in hypoglycaemia (<2.8mmol/L) 
o %time in hypoglycaemia (<3.3mmol/L) 
o %time in hypoglycaemia (<3.9mmol/L) 
o %time in target (3.9-10mmol/L) 
o %time spent in hyperglycaemia (>10mmol/L) 
o Measures of glycaemic variability  
o Mean glucose 
o Glucose SD 
• 
Severe hypoglycaemia 
• 
Insulin outcomes 
o Number of insulin time blocks changed 
o Number of insulin basal rate changes 
o Change to total daily insulin dose 
• 
Basal insulin:bolus insulin ratio 
• 
Healthcare professional qualitative feedback 
 
 
4. PARTICIPANT ENTRY 
4.1 PRE-REGISTRATION EVALUATIONS 
 
• 
HbA1c 
• 
Serum C-peptide 
• 
Plasma glucose 
• 
Coeliac screen 


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• 
Gastroparesis screen 
 
 
• 
Thyroid function tests 
• 
GOLD hypoglycaemia score 
 
4.2 INCLUSION CRITERIA 
 
• 
Adults ≥18 years of age 
• 
Diagnosis of T1DM for > 1 year  
• 
On MDI with decision made to commence CSII 
• 
Structured education in previous 3 years 
• 
HbA1c ≤ 75mmol/mol (9%) 
• 
Stimulated c-peptide <200pmol/L 
• 
No severe hypoglycaemia (defined as needing 3rd party assistance) in previous year 
 
4.3 EXCLUSION CRITERIA 
 
• 
Previous CSII 
• 
Night or shift worker 
• 
Recurrent severe hypoglycaemia 
• 
Pregnant or planning pregnancy 
• 
Breastfeeding 
• 
Enrolled in other clinical trials 
• 
Have active malignancy or under investigation for malignancy 
• 
Addison’s Disease 
• 
Gastroparesis 
• 
Autonomic neuropathy 
• 
Concomitant use of GLP-1 analogues and gliptins 
• 
Visual impairment 
• 
Reduced manual dexterity 
 
Any participant who is excluded at screening will be replaced by another participant. 
 
4.4 WITHDRAWAL CRITERIA 
 
• 
Loss of capacity to give informed consent 
• 
Recurrent severe hypoglycaemia 
• 
Terminal illness 
 
Withdrawal will be immediate and subjects will be followed up in the appropriate out-patient 
diabetes clinic within 4 weeks of withdrawal. 
 
 
5. ADVERSE EVENTS 
5.1 DEFINITIONS 
Adverse Event (AE): any untoward medical occurrence in a patient or clinical study 
subject. 
 


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IRAS ID: 237129 
 
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence 
or effect 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 were more severe 
• 
Requires hospitalisation, or prolongation of existing inpatients’ 
hospitalisation 
• 
Results in persistent or significant disability or incapacity 
• 
Is a congenital anomaly 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 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. 
 
5.2 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. 
 
5.2.1 Non serious AEs 
All such events, whether expected or not, should be recorded. 
 
5.2.2 Serious AEs 
An SAE form should be completed and faxed to the Chief Investigator 
within 24 hours. 
 
All SAEs should be reported to the <name of REC> where in the opinion 
of the Chief Investigator, the event was: 
• 
‘related’, ie resulted from the administration of any of the research 
procedures; and 
• 
‘unexpected’, ie 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 for non-IMP studies. The Chief Investigator must also 
notify the Sponsor of all SAEs. 
 
Local investigators should report any SAEs as required by their Local 
Research Ethics Committee, Sponsor and/or Research & Development 
Office. 


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
 
 
 
 
Contact details for reporting SAEs 
Fax: xxx, attention xxx 
Please send SAE forms to: xxx 
Tel: xxx (Mon to Fri 09.00 – 17.00) 


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
 
6. ASSESSMENT AND FOLLOW-UP 
 
 
Usual pre-pump assessment and screening 
Anyone who is being considered for insulin pump therapy will be assessed by their usual care 
team to complete documentation for funding and to take some blood samples to measure 
HbA1c, glucose, kidney function, serum C-peptide, coeliac antibodies and thyroid function test. 
A urine sample will be taken to do a pregnancy test in woman of child bearing age. A medical 
and medication history will be taken. Validated questionnaires will be used to screen for 
gastroparesis and hypo unawareness. An insulin pump will be demonstrated and the pros and 
cons of insulin pump will be explained to ensure a fully informed decision about commencing 
insulin pump therapy is made. At this appointment potential participants will be provided with 
a participant information sheet to read in their own time.  
 
At least 24 hours after this appointment potential participants will be contacted to see whether 
they want to continue with insulin pump therapy, and if so, whether they would like to do this 
under their usual care team, or under the research team in this trial. This appointment usually 
takes between 30 and 60 minutes. 
 
Visit 1 - Informed consent - 30 minutes 
Following informed consent, participants will be screened as per inclusion and exclusion 
criteria. This appointment will take up to 30 minutes. Participants will be provided with a 
capillary blood glucose monitor to use throughout the study if they do not already have one.  
 
Visit 2 – Pre-pump CGM – 60 minutes 
Participants will be taught to insert and replace a Dexcom G4 sensor for use with blinded 
CGM. They will be asked to wear it for one week prior pump initiation, and continuously after 
pump initiation until the end of the study. Each sensor lasts for 7 days so participants will 
learn to replace them themselves. They will be asked to keep a food and exercise diary 
during the pre-pump CGM week, and during week 4 of insulin pump therapy. Participants will 
be given copies of the data from the CGM at the end of the study. Diabetes self-
management will continue as usual. Participants will be asked to complete questionnaires to 
measure awareness of hypoglycaemia (Gold), hypoglycaemia fear (HFS), general quality of 
life (WHOQoLBref), diabetes distress (DDS-2) and diabetes quality of life (DQOL), which will 
be repeated at the end of the study. Self-help leaflets from Diabetes UK will be available in 
case participants find these questionnaires distressing, and can approach the researcher for 
signposting for further help. During this session participants will be randomised to a flat basal 
rate or circadian rate (defined by Roche Accu-Chek software using a predefined algorithm).  
  
Visit 3 – CSII initiation– 3-4 hours 
Participants will initiate CSII in pairs from the same randomisation group, at the metabolic day 
ward in St Mary’s hospital on a Monday. They will be taught how to use their insulin pump by 
a diabetes specialist dietitian trained in insulin pump therapy. They will be asked to take half 
their usual background insulin the night before, or to exclude the morning dose if they are on 
twice daily background insulin. Participants will learn to set up the pump, insert the cannula, 
and learn how to make adjustments to the settings. Both arms will receive half of 75% of their 
pre-pump total daily insulin dose via basal rates. These basal rates will be calculated in 
advance ready for programming at the CSII initiation visit. 
 
Participants will receive the research dietitian’s contact details for queries in working hours, 
and will be given a 24 hour product support number in case of pump failure.  They will receive 


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
structured information on what to do manage high and low blood glucose levels. They will be 
instructed to return to injections in case of pump failure. 
 
Between visits 3 and 4 
Participants will be asked to record their blood glucose levels using capillary blood glucose 
testing a minimum of four times per day – before meals, before bed, and if they feel unwell.  
These results will be reviewed by the researcher via telephone on day 1, 2 and 4 of pump 
therapy, and insulin pump settings will be adjusted if needed, based on the criteria below:. 
 
1. Insulin to carbohydrate ratios will be changed by 10% in the event of two values being 
<4mmol/l within four hours of the meal, or >12mmol/l 4 hours after the meal, in the absence 
of a precipitating factor2. Insulin basal rates will only be adjusted in the case of: 
• 
Severe hypoglycaemia 
• 
Recurrent hypoglycaemia (<4mmol/L) at the same time on 3 consecutive days 
• 
Recurrent hyperglycaemia (>12mmol/L) at the same time on 3 consecutive days 
 
The use of temporary basal rates during exercise and activity will be standardised. Participants 
will be asked to refrain from exercising and using temporary basal rates during the fasting 
basal rate testing. 
 
Fasting basal rate tests 
 
Participants will undertake a series of fasting basal rate testing commencing on day 7, 14 and 
28 of insulin pump therapy. The basal rate testing protocol is as follows: 
 
Day 1 Overnight testing with self-monitoring at 22:00, 00:00, 02:00, 04:00 and 06:00 
Day 2 Omit breakfast with self-monitoring at 06:00, 08:00, 10:00: 12:00 
Day 3 Omit lunch with self-monitoring at 12:00, 14:00, 16:00, 18:00 
Day 4  Omit evening meal with self-monitoring at 18:00, 20:00, 22:00, 00:00, 02:00, 04:00, 
06:00 
 
 
Visit 4 and 5 (Day 11 and 18 of pump therapy) 
Insulin pumps and CGM will be downloaded, and insulin basal rates will be adjusted based on 
the fasting basal rate testing as follows: 
• 
Glucose rise more than 1.7mM during sleep or over a 4 hour period when fasting, 
increase basal rate by 10% for 2 hours at start of rise 
• 
Glucose fall more than 1.7mM during sleep or over a 4 hour period when fasting, 
reduce basal rate by 10% for 2 hours at start of fall 
 
Visit 6 (Around day 32 of insulin pump therapy) 
Insulin pump and CGM will be downloaded. Participants will be asked to repeat the 
questionnaires to measure awareness of hypoglycaemia (Gold), hypoglycaemia fear (HFS), 
general quality of life (WHOQoLBref), diabetes distress (DDS-2) and diabetes quality of life 
(DQOL).  Blood samples to repeat HbA1c will be taken. Pump and CGM downloads will be 
reviewed, and pump settings adjusted to optimise blood glucose control. 
 
At the end of the study, participants will continue using their insulin pumps if they wish, but 
will return the CGM. They will be followed up in specialist type 1 insulin pump clinics, as per 
usual care. 
 
Blood samples will be analysed in the Imperial College Healthcare NHS Trust laboratory and 
discarded after analysis.  


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
 
7. STATISTICS AND DATA ANALYSIS 
 
This is a single site randomised study with an intervention group and a control group. The 
primary outcome is absolute change in insulin basal rate over 24 hours after 3 rounds of basal 
rate testing (calculated by the sum of absolute changes for each 1 hour block compared with 
baseline). This is a pilot study and will demonstrate the effect size of circadian basal rates. A 
post hoc power calculation will be performed. 
 
The sample size is comparable to other diabetes technology studies, and is a realistic number 
for recruitment in the time period. In 2015-2016 47 people with type 1 diabetes commenced 
insulin pump therapy at Imperial College. 
 
Data will be entered onto a database with restricted fields by the research team and, following 
data checking and cleaning, analysis will be conducted using Stata statistical software. 
Analysis will be conducted by Dr Oliver, Dr Ian Godsland (Reader in Human Metabolism) and 
the Imperial College Statistics Service. The primary and secondary outcomes will be analysed 
by intention to treat analysis. The difference in basal rate change between the two groups at 
the endpoint will be assessed by a two-tailed independent t test. Secondary outcomes will be 
assessed by independent t test or, if data are non-parametric, a Mann-Whitney U test. Missing 
data will be minimised by reducing manual data entry, using technology to collect glucose 
data, and by carefully supporting participants. Where present, missing data will be handled by 
full analysis of the available data only.  
 
Data and all appropriate documentation will be stored for a minimum of 10 years after the 
completion of the study, including the follow-up period. Anonymised data will be kept on 
university password-protected computers in a locked room. Access is only available to the 
clinical research team. The identifier codes will be kept on password-protected NHS 
computers. The anonymised data includes CGM data, food and exercise diaries and blood 
test. 
 
The paper copies of the consent forms and questionnaires will be kept in a specifically labelled 
FIRST1D file in a locked cupboard in the diabetes research office  
 
 
8. REGULATORY ISSUES 
8.1 ETHICS APPROVAL 
The Chief Investigator has obtained approval from the xxx Research Ethics Committee and 
the HRA. The study must be submitted for confirmation of capacity and capability (CCC) at 
each participating NHS Trust. 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. 
 
8.2 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 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 these cases the participants remain within the study for the purposes of follow-up 


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
and data analysis. All participants are free to withdraw at any time from the protocol treatment 
without giving reasons and without prejudicing further treatment. 
 
8.3 CONFIDENTIALITY 
The Chief Investigator will preserve the confidentiality of participants taking part in the study 
and is registered under the Data Protection Act. 
 
8.4 INDEMNITY 
Imperial College London holds negligent harm and non-negligent harm insurance policies 
which apply to this study 
 
8.5 SPONSOR 
Imperial College Londonwill act as the main Sponsor for this study. Delegated responsibilities 
will be assigned to the NHS trusts taking part in this study. 
 
8.6 FUNDING 
Roche are funding this study. Travel expenses will be provided for participants of the study.  
 
8.7 AUDITS 
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). 
 
 
9. STUDY MANAGEMENT 
The day-to-day management of the study will be co-ordinated Sian Rilstone 
 
10. 
PUBLICATION POLICY 
 
Data from the study will be analysed then published in peer-reviewed scientific journals and 
presented at Scientific Conferences. A lay summary of the data will be disseminated to all 
participants and a summary of results will be publically available. 
 
 
11. 
REFERENCES 
1. 
Freckmann G, Jovanovic L, Baumstarck A, Haug C, ven der Hem W. The Circadian 
Study: the get-up phenomenon in type 1 diabetes. Diabetes Care 2008;31:e85 
2. 
Lüddeke HJ, Renner R, Hepp D. [Analyse von Basalratenprofilen und Bolusabruf 
bezuglich HbA1c und Hypoglykänierate für IDDM-Patienten unter CSII-Therapie mit 
multiprogrammierbaren Pumpen. Welches Basalrateprofil ist optimal?] Diabetes 
Stoffwechsel 1994;178 
3. 
Wizemann E, Renner R, Hepp KD. Prospective Evaluation of a standardized basal rate 
distribution for CSII in type 1 diabetes over 6 months. Diabetes Stoffwechsel 
2001;10(supp 1):57 
4. 
Hunger-Dathe W, Illner N, Müller UA, Samann A. [Kein Vorteil einer chronomodulierten 
im Vergleich zur oligophasischen Baslrateprogrammierung bei Patienten mit Diabetes 
mellitus Typ 1 und kontinuierlicher subkutaner Insulininfusionstherapie (CSII)]. 
Diabetes Stoffwechsel 2003;12:101 


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12. 
Appendices 
 
1. Summary of investigation, treatment and assessments 
2. Participant information sheet 
3. Consent form 
4. GP letter 
5. Participant invite letter 
6. Questionnaire to measure awareness of hypoglycaemia (Gold) 
7. Questionnaire to measure Hypoglycaemia fear (HFS) 
8. Questionnaire to measure General quality of life (WHOQoLBref) 
9. Questionnaire to measure Diabetes distress (DDS) 
10. Questionnaire to measure Diabetes QoL (DQOL) 
 
 
 
 


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
Appendix 1. Summary of investigations, treatment and assessments 
 
 
 
Days post CSII initiation 
Usual pre 
pump 
assessment 
and 
screening 
appointment 
Informed 
consent 
appointment 
Pre-
randomisa
tion 
0 
7 
14 
28 
 
Informed consent 
 
X 
 
 
 
 
 
Blood tests (Thyroid 
function tests, coeliac 
serology, plasma 
glucose, serum c-
peptide) 
X 
 
 
X 
HbA1c (blood test) 
X 
 
 
 
X 
GOLD score 
questionnaire 
X 
 
 
X 
Blinded CGM 
 
 
X 
X 
X 
X 
X 
Psychosocial 
questionnaires 
 
 
X 
 
X 
Basal rate testing 
 
 
 
 
X 
X 
X 
Pump download 
 
 
 
 
X 
X 
X 
 
 
Appendix 2. Participant information sheet 
 
Appendix 3. Consent form 
 
Appendix 4. GP letter 
 
Appendix 5. Participant invite letter 
 
Appendix 6. Questionnaire to measure awareness of hypoglycaemia (Gold) 
 
Appendix 7. Questionnaire to measure Hypoglycaemia fear (HFS-II) 
 
Appendix 8. Questionnaire to measure general quality of life (WHOQoLBref) 
 
Appendix 9. Questionnaire to measure Diabetes distress (DDS) 
 


FIRST1D protocol v1.7 23.2.18 
IRAS ID: 237129 
 
Appendix 10. Questionnaire to measure Diabetes QoL (DQOL)