Additional identifiers
EudraCT number
2013-004264-60
ClinicalTrials.gov number
Protocol/serial number
19156
Study information
Scientific title
Compensatory changes in energy balance during dapagliflozin treatment in type 2 diabetes
Acronym
ENERGIZE
Study hypothesis
This study is designed to study the mechanisms underlying the changes in energy balance that occur with dapagliflozin treatment for type 2 diabetes (T2DM), so that in the future it might be possible to develop interventions to optimise weight loss and therefore therapeutic benefit of this agent.
Ethics approval
First MREC approval date 09/06/2014, ref: 14/NW/0340
Study design
Randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
Topic: Diabetes; Subtopic: Type 2; Disease: Diabetic Control, Metabolic, Nutrition, Obesity
Intervention
1. Dapagliflozin 10mg /day or matching placebo administered orally (double-blind) crossover design
2. Short-term (2 x 7 day periods) evaluation
3. Long-term (2 x 12 weeks periods) evaluation
4. 26 weeks treatment in total)
5. Study Entry : Single Randomisation only
Intervention type
Drug
Phase
Phase IV
Drug names
Dapagliflozin
Primary outcome measures
To evaluate the effect of dapagliflozin 10mg daily compared to placebo
Secondary outcome measures
N/A
Overall trial start date
30/06/2015
Overall trial end date
31/12/2016
Reason abandoned
Eligibility
Participant inclusion criteria
1. Type 2 diabetes, either treated with diet alone or up to 2 other oral agents (excluding pioglitazone) with an HbA1c > 7.5% (58mmol/mol) and <11% (97 mmol/mol)
2. BMI 20-50kg/m2
3. Men and women, Age 18-75
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 52; UK Sample Size: 52; Description: primary outcome measure is energy intake(g) after 12weeks.52 subjects are required in order to detect a 12.5% change with 80% power and at a two-sided 5% level of significance using the method for a paired t-test.This estimate assumes a correlation between measurements of 0.7 and a between-subject standard deviation of 165.The change in energy intake of 12.5% is based on a baseline level of 460g.This allows for a drop-out rate of 20% and was calculated using PROC POWER in SAS 9.3
Participant exclusion criteria
1. Medical History and Concurrent Diseases:
1.1. Type 1 diabetes mellitus
1.2. History of diabetic ketoacidosis or hyperosmolar nonketotic coma
1.3. Hyperthyroidism
1.4. Hypothyroidism (subjects with a normal TSH and free T4, and on a stable dose of thyroxine for at least 3 months may be included)
1.5. Uncontrolled hypertension (blood pressure >150/90 mmHg)
1.6. Recent (< 6 months) myocardial infarction
1.7. Previous stroke
1.8. Significant cardiac dysrhythmias (including pacemaker or ICD)
1.9. Known chronic liver disease (other than hepatic steatosis)
1.10. Familial renal glycosuria
1.11. History of seizures or unexplained syncope
1.12. Pregnancy
1.13. Recent major change in body weight (> 3kg loss or gain in preceding month)
1.14. Patients with very low BMI (<20kg/m2)
1.15. History of malignancy
1.16. Presence of any other medical condition that would, in the opinion of the investigator preclude safe participation in the study
1.17. Alcohol consumption in excess of daily recommended limits (14 units/week females, 21 units/week males)
1.18. Any history of internal metal, pacemakers, or ferromagnetic metallic implants intraocular foreign bodies or cerebral aneurysm clips (exclusion from MR scanning)
2. Physical and Laboratory Test Findings:
2.1. ALT > 3 x ULN
2.2. AST > 3 x ULN
2.3. Bilirubin > 2 x ULN
2.4. Haemoglobin = 10.5 g/dL (= 105 g/L) for men; haemoglobin = 9.5 g/dL (= 95 g/L) for women
2.5. eGFR <60 ml /min
2.6. Unexplained haematuria
2.7. Weight > 150kg (due to limitations of MRI scanner)
3. Allergies and Adverse Drug Reactions:
3.1. Subjects with a history of any serious hypersensitivity reaction to dapagliflozin or SGLT-2 inhibitor
3.2. Subjects who are allergic or intolerant to any of the study foods in accordance with the Screening questionnaire
4. Sex and Reproductive Status – see below:
4.1. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the study duration plus 8 weeks
4.2. Women who are pregnant or breastfeeding
4.3. Sexually active fertile men not using effective birth control if their partners are WOCBP
5. Prohibited Treatments and/or Therapies:
5.1. Diabetes treated with pioglitazone, GLP-1 analogues or insulin or any other SGLT-2 inhibitor
5.2. Use of other weight loss medication or any drug that might affect body weight or appetite (including anti-depressants, antipsychotics, corticosteroids)
5.3. Patients who are receiving dapagliflozin
5.4. Patients who have participated in a SGLT2 clinical trial within the past 30 days.
5.5. Patients who are currently receiving a loop diuretic
6. Other Exclusion Criteria:
6.1. Prisoners or subjects who are involuntarily incarcerated.
6.2. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.
Eligibility criteria for this study have been carefully considered to ensure the safety of the study subjects and to ensure that the results of the study can be used. It is imperative that subjects fully meet all eligibility criteria.
Recruitment start date
03/08/2015
Recruitment end date
31/12/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Cancer Research UK
Liverpool CR-UK Centre - Waterhouse Building
1-3 Brownlow Street
Liverpool
L69 3GL
United Kingdom
Funders
Funder type
Industry
Funder name
AstraZeneca
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2017 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/28132008