Diabetes Mellitus, Type 2Phase 4@HOMENCT06374043
Decentralized N=1 Study: A Feasible Approach to Evaluate Individual Therapy Response to Dapagliflozin.
A Phase 4 study testing Dapagliflozin 10mg Tab, Withings BPM Connect and Withings Body+ in people with Diabetes Mellitus, Type 2 and Diabetes Mellitus Type 2 With Proteinuria, run by University Medical Center Groningen at 2 sites in Netherlands.
Trial summary
Randomized placebo-controlled double-blind cross-over N=1 trial in adult male and female patients with UACR >20 mg/g (2.26 mg/mmol) with type 2 diabetes treated in primary or secondary healthcare. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2, Diabetes Mellitus Type 2 With Proteinuria, Diabetes Mellitus
- What is being tested?
- Dapagliflozin 10mg Tab, Withings BPM Connect and Withings Body+
- Type of treatment
- Pill or oral medicine, Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 2 sitesNetherlands
- Study dates
- 11 May 2021to 13 Sep 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Diagnosis of type 2 diabetes mellitus
- Urinary albumin-to-creatinine ratio >20 mg/g (2.26 mg/mmol)
- eGFR >30 ml/min/1.73m2
- Willing to sign informed consent
Who cannot join
- Diagnosis of type 1 diabetes
- Prior treatment with SGLT2 inhibitor in the four weeks prior to randomization
- History of severe hypersensitivity or contraindications to dapagliflozin
- Unable to monitor blood pressure / body weight or handle digital technologies
- History of non-adherence to medical regimens or unwillingness to comply with the study protocol
- Participation in any clinical investigation within 3 months prior to initial dosing
Show all 24Show fewer
- Unstable or rapidly progressing renal disease
- Severe hepatic impairment (Child-Pugh class C) as determined by the treating physician.
- Active malignancy
- Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following: History of active inflammatory bowel disease, within the last six months; Major gastrointestinal tract surgery as decided by the treating physician; Pancreatitis within the last six months; Evidence of serious hepatic disease as determined by the treating physician; Evidence of urinary obstruction or difficulty in voiding at screening.
- Confirmed lactose intolerance demonstrated with a lactose intolerance test.
- Donation or loss of 400 mL of blood within 8 weeks prior to initial dosing
- History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening
- Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
- Current pregnancy or breast feeding / attempting to conceive.
- Women of childbearing potential (WOCBP): WOCBP who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study drug in such a manner the risk of pregnancy is minimized; WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent of HCG) within 0 to 72 hours before the first dose of study drug.
- WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal (see definition below). The following women are WOCBP:
- Women using the following methods to prevent pregnancy: oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as intrauterine devices or barrier methods (diaphragm, condoms, spermicides).
- Women who are practicing abstinence.
- Women who have a partner who is sterile (e.g. due to vasectomy).
- Post-menopause is defined as:
- Women who have had amenorrhea for >12 consecutive months (without another cause) and who have a documented serum follicle-stimulating hormone (FSH) level >35 mIU/mL.
- Women who have irregular menstrual periods and a documented serum FSH level >35 mIU/mL.
- Women who are taking hormone replacement therapy (HRT).
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Ziekenhuisgroep Twente
Almelo
University Medical Center Groningen
Groningen
About this study
Official title: Individual Albuminuria Lowering Response to Dapagliflozin in a Decentralized Clinical Trial in Patients With Type 2 Diabetes Mellitus and Elevated Albuminuria
Randomized placebo-controlled double-blind cross-over N=1 trial in adult male and female patients with UACR >20 mg/g (2.26 mg/mmol) with type 2 diabetes treated in primary or secondary healthcare.
The goal of this clinical trial is to determine the individual response to the SGLT2 inhibitor dapagliflozin in urine albumin-to-creatinine ratio (UACR). Secondary objectives are to determine the individual response to dapagliflozin in systolic blood pressure, body weight, eGFR, and fasting plasma glucose.
Read more
Participants will collect all study data in the comfort of their own environments:
- First-morning void urine samples
- Capillary blood samples
- Blood pressure
- Body weight
Participants will be randomly assigned to a cross-over study consisting of two periods of 1-week treatment with dapagliflozin 10 mg/day and two periods of 1-week treatment with placebo in random order with a 1-week wash-out period between every treatment period to avoid cross-over effects.
Read the detailed description
Rationale:
Persistent increased albuminuria is a strong risk marker for progressive kidney disease and cardiovascular disease in patients with or without diabetes. The degree of albuminuria reduction in the first months of treatment with pharmacological or dietary intervention correlates with the degree of long-term (3 to 4 years) renal or cardiovascular protection. Despite the various available treatments to decrease urinary albumin excretion, residual albuminuria persists in many patients. The high residual albuminuria in a proportion of patients is at least in part explained by suboptimal response to the current treatments (i.e., ACE inhibitor or Angiotensin Receptor Blockers).
Dapagliflozin is a sodium-glucose transport inhibitor and inhibits the reabsorption of glucose in the proximal tubule. This leads to a decrease in fasting plasma glucose and HbA1c in patients with type 2 diabetes. In addition, dapagliflozin administration causes a decrease in blood pressure and body weight and an increase in hematocrit suggestive of a diuretic effect. Previous studies have also demonstrated the albuminuria lowering effects of dapagliflozin in patients with type 2 diabetes mellitus.
Although dapagliflozin markedly slows progression of kidney function decline (and reduces cardiovascular outcomes) on a population level, randomized parallel group trials have suggested a marked variation in the response to dapagliflozin between individual patients. By design, randomized parallel group placebo-controlled clinical trials test the efficacy of new interventions on a population level but do not assess the efficacy of a drug for the individual. Although there is variation in response between patients, parallel group trial does not allow conclusions whether this variation is a true variation in drug response, or measurement or temporal random variation. The investigators therefore propose a cross-over trial with repeated administration (i.e., a series of N=1 trials) to ascertain the individual drug response. This design specifically allows for assessment of drug efficacy and safety at an individual level.
Objectives:
- Primary: To determine the individual response to the SGTL2 inhibitor dapagliflozin in urine albumin-to-creatinine ratio (UACR)
- Secondary: To determine the individual response to the SGLT2 inhibitor dapagliflozin in: systolic blood pressure, body weight, eGFR, fasting plasma glucose
Study design:
Randomized placebo-controlled double-blind cross-over N=1 trial. Eligible participants will be invited for screening. After a screening visit, eligible patients will be randomly assigned to a cross-over study consisting of two periods of 1-week treatment with dapagliflozin and two periods of 1-week treatment with placebo in random order with a 1-week wash-out period between every treatment period to avoid cross-over effects. Based on a prior study where patients were exposed to dapagliflozin 10 mg, effects of dapagliflozin on UACR, blood pressure, body weight, eGFR and plasma glucose were fully present after 1 week and returned to baseline 4 days after drug discontinuation. Hence, a 1-week treatment followed by 1 week wash-out is considered sufficient to detect treatment effects.
Study population:
Adult male and female patients with UACR >20 mg/g (2.26 mg/mmol) with type 2 diabetes mellitus treated in primary or secondary healthcare. Subjects will be recruited via general practitioner practices and via the outpatient clinic of the Department of Internal Medicine of the Ziekenhuisgroep Twente, Almelo.
Intervention:
Dapagliflozin 10 mg/day
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
The efficacy and safety of dapagliflozin is established in multiple parallel randomized controlled trials involving more than 25,000 patients with type 2 diabetes. Urinary tract infections and genital infections are the most frequently reported side effects. Dapagliflozin reduces body weight unlike sulfonylurea derivatives and insulin.
Participants visit the outpatient clinic at three occasions (i.e., a screening visit, a second visit and end of study visit) and have to record body weight and blood pressure at home and collect blood and urine at home.
Blood pressure and body weight are measured at home by the participants using ambulant devices (Withings BPM Connect and Withings Body+, respectively). Participants measure their blood pressure and body weight once daily on 28 and 40 days in total, respectively. Capillary blood will be sampled at home by participants using a BD Microtainer® Contact-Activated Lancet (once daily on 22 days in total). Blood is collected with the Hem-Col® device, which is designed to collect capillary blood drawn with a finger prick. In order to make patients comfortable with the blood collection procedures, they first collect a capillary blood sample at the study site during the second visit under supervision of trained lab technicians. A venous blood sample will also be taken during the second visit in order to compare the clinical chemistry assessments in capillary blood with those measured in venous blood samples (NL70447.100.19). Participants will be asked to draw blood samples at home by a finger prick and send the samples to the laboratory. Participants will collect first morning void urine samples through the PeeSpot® device (once daily on 40 days in total) which allows for decentralized urine collection in a small tube. The urine tubes and blood samples will be sent by regular mail to the laboratory. No other invasive measurements will be executed.
The advantage of an N=1 study is that efficacy of the intervention is vetted for the actual participant. Dapagliflozin is currently marketed in the Netherlands and recommended in patients with type 2 diabetes mellitus and eGFR>45 mL/min/1.73m2. Patients who show a satisfactory response to dapagliflozin and whose characteristics fulfill the criteria according to which dapagliflozin can be prescribed in clinical practice are offered to receive dapagliflozin after the study. It is expected that the indication for dapagliflozin will be broadened to patients with eGFR 25-45 mL/min/1.73m2 in the near future. If this occurs, these patients can also be treated on-label in practice.
The expected time investment for participants is 20 hours, including measurements at home. Participants receive restitution of travel costs to visit the outpatient clinic for the screening, randomization and end of study visit. Participants receive no priority in treatment of other diseases in the clinic during this study. Participation in this study is on a free-will base. Participants can keep the body weight scale and blood pressure device at the end of the study.
- Conditions
- Diabetes Mellitus, Type 2, Diabetes Mellitus Type 2 With Proteinuria, Diabetes Mellitus, Diabetes, Diabetes Complications, Albuminuria
- Being tested
- Dapagliflozin 10mg Tab, Placebo, Withings BPM Connect, Withings Body+, Hem-Col Capillary Blood Collection Device
- Keywords
- Type 2 diabetes, Diabetes Mellitus, Type 2, Albuminuria, Diabetes Mellitus, Diabetes Mellitus Type 2 with Proteinuria, Personalized Medicine, Decentralized, Remote clinical trial, Remote data collection, Individualized, CKD, Chronic Kidney Disease, Albuminuria-Lowering therapies, Dapagliflozin, SGLT2 inhibitor, Placebo-controlled, Randomized, Cross-over, N=1, N-1
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus, Diabetes Complications, Albuminuria, Renal Insufficiency, Chronic, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 10mg TabDrug
Also called Forxiga, (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, A10BK01
Oral administration
PlaceboDrug
Oral administration
Withings BPM ConnectDevice
CE marked and clinically validated blood pressure monitor. Clinical trial results are within the margin of acceptance defined by the internationally recognized evaluation standard of blood pressure monitors ANSI/AAMI/ISO 81060-2:2013, EN ISO 81060-2:2014, developed by the European Society of Hypertension, British Hypertension Society and Association for the Advancement of Medical Instrumentation/American Heart Association.
Blood pressure will be measured by the participants once daily on 28 days. Three consecutive measurements are taken.
Withings Body+Device
CE marked and clinically validated advanced Wi-Fi smart scale.
Body weight will be measured by the participants once daily on 40 days.
Hem-Col Capillary Blood Collection DeviceDiagnostic test
Capillary blood samples will be obtained using a BD Microtainer® Contact-Activated Lancet (Franklin Lakes, New Jersey, USA) once daily on 22 days. These blood samples will be collected into Hem-Col® tubes (Hem-Col, Labonovum, Limmen, the Netherlands), specifically designed for collection of capillary blood acquired through a finger prick. The Hem-Col microtube is equipped with an anticoagulant and a preservation buffer, enhancing the stability of analytes in whole blood. These Hem-Col tubes have the dimensions of standard blood collection tubes and are constructed from polyethylene, featuring a pierceable cap made of thermoplastic elastomers. Each tube incorporates a liquid barrier, with the inner part preventing the loss of Hem-Col preservation fluid and the outer part serving as a scoop for collecting blood from a finger prick. The Hem-Col lithium heparin tubes will be utilized for the analysis of creatinine, CRP, lipid profile, HbA1c, uric acid, glucose and NT-proBNP.
MEMS (Medication Electronic Monitoring System) CapDevice
Medication will be provided in standard medicine bottles with the MEMS® (Medication Electronic Monitoring System) Cap (AARDEX Ltd, Union City, CA, USA), which is a customizable medication package which records and stores up to 4,000 dosing events. The cap fits on standard medicine bottles and with integrated microcircuits, the child-resistant MEMS® Cap records the date and time whenever a patient opens a vial. The stored information can be transferred at any time through the MEMS® Reader to the adherence software for immediate analysis and interpretation.
Questionnaire: participants' perspectives toward remote data collectionBehavioural
Self-made questionnaires consisting of 6 multiple choice questions and 2 open questions will be used to assess patient experience and satisfaction to guide and inform future trials and use in clinical practice.
| Study group | Role | What they receive |
|---|---|---|
| Option 1 (D-D-P-P) | Other | Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Placebo Week 8. Wash-out Receives: Drug: Dapagliflozin 10mg Tab; Drug: Placebo; Device: Withings BPM Connect; Device: Withings Body+; Diagnostic Test: Hem-Col Capillary Blood Collection Device; Device: MEMS (Medication Electronic Monitoring System) Cap; Behavioral: Questionnaire: participants' perspectives toward remote data collection |
| Option 2 (D-P-D-P) | Other | Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out Receives: Drug: Dapagliflozin 10mg Tab; Drug: Placebo; Device: Withings BPM Connect; Device: Withings Body+; Diagnostic Test: Hem-Col Capillary Blood Collection Device; Device: MEMS (Medication Electronic Monitoring System) Cap; Behavioral: Questionnaire: participants' perspectives toward remote data collection |
| Option 3 (D-P-P-D) | Other | Week 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out Receives: Drug: Dapagliflozin 10mg Tab; Drug: Placebo; Device: Withings BPM Connect; Device: Withings Body+; Diagnostic Test: Hem-Col Capillary Blood Collection Device; Device: MEMS (Medication Electronic Monitoring System) Cap; Behavioral: Questionnaire: participants' perspectives toward remote data collection |
| Option 4 (P-P-D-D) | Other | Week 1. Placebo Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out Receives: Drug: Dapagliflozin 10mg Tab; Drug: Placebo; Device: Withings BPM Connect; Device: Withings Body+; Diagnostic Test: Hem-Col Capillary Blood Collection Device; Device: MEMS (Medication Electronic Monitoring System) Cap; Behavioral: Questionnaire: participants' perspectives toward remote data collection |
| Option 5 (P-D-P-D) | Other | Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out Receives: Drug: Dapagliflozin 10mg Tab; Drug: Placebo; Device: Withings BPM Connect; Device: Withings Body+; Diagnostic Test: Hem-Col Capillary Blood Collection Device; Device: MEMS (Medication Electronic Monitoring System) Cap; Behavioral: Questionnaire: participants' perspectives toward remote data collection |
| Option 6 (P-D-D-P) | Other | Week 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out Receives: Drug: Dapagliflozin 10mg Tab; Drug: Placebo; Device: Withings BPM Connect; Device: Withings Body+; Diagnostic Test: Hem-Col Capillary Blood Collection Device; Device: MEMS (Medication Electronic Monitoring System) Cap; Behavioral: Questionnaire: participants' perspectives toward remote data collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
UACR response
The individual response to the SGLT2 inhibitor dapagliflozin in urine albumin-to-creatinine ratio (UACR)
Measured: Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.
Secondary outcomes (4)
Systolic blood pressure response
The individual response to the SGLT2 inhibitor dapagliflozin in systolic blood pressure.
Measured: Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.
Body weight response
The individual response to the SGLT2 inhibitor dapagliflozin in body weight.
Measured: Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.
eGFR response
The individual response to the SGLT2 inhibitor dapagliflozin in eGFR.
Measured: Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.
Fasting plasma glucose response
The individual response to the SGLT2 inhibitor dapagliflozin in glucose.
Measured: Will be assessed within 6 months and reported within 2 years after conclusion of the study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2024
- Study start11 May 2021
- Primary completion13 Sep 2022
- Study completion13 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized placebo-controlled double-blind cross-over trial with repeated administration (i.e., a series of N=1 trials).
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06374043
- Sponsor's protocol ID
- 2020/1002
- Acronym
- @HOME
- Status last verified
- Apr 2024
- First submitted
- 15 Apr 2024
- Last updated
- 22 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Individual Albuminuria Lowering Response to Dapagliflozin in a Decentralized Clinical Trial in Patients With Type 2 Diabetes Mellitus and Elevated Albuminuria
- ClinicalTrials.gov ID
- NCT06374043
- Acronym / sponsor ID
- @HOME / 2020/1002
- Conditions
- Diabetes Mellitus, Type 2, Diabetes Mellitus Type 2 With Proteinuria, Diabetes Mellitus, Diabetes, Diabetes Complications, Albuminuria
- Keywords
- Type 2 diabetes, Diabetes Mellitus, Type 2, Albuminuria, Diabetes Mellitus, Diabetes Mellitus Type 2 with Proteinuria, Personalized Medicine, Decentralized, Remote clinical trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 11 May 2021 (actual)
- Primary completion
- 13 Sep 2022 (actual)
- Study completion
- 13 Sep 2022 (actual)
- First posted
- 18 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomized placebo-controlled double-blind cross-over N=1 trial in adult male and female patients with UACR >20 mg/g (2.26 mg/mmol) with type 2 diabetes treated in primary or secondary healthcare.
The goal of this clinical trial is to determine the individual response to the SGLT2 inhibitor dapagliflozin in urine albumin-to-creatinine ratio (UACR). Secondary objectives are to determine the individual response to dapagliflozin in systolic blood pressure, body weight, eGFR, and fasting plasma glucose.
Participants will collect all study data in the comfort of their own environments:
- First-morning void urine samples
- Capillary blood samples
- Blood pressure
- Body weight
Participants will be randomly assigned to a cross-over study consisting of two periods of 1-week treatment with dapagliflozin 10 mg/day and two periods of 1-week treatment with placebo in random order with a 1-week wash-out period between every treatment period to avoid cross-over effects.
Detailed description
Rationale:
Persistent increased albuminuria is a strong risk marker for progressive kidney disease and cardiovascular disease in patients with or without diabetes. The degree of albuminuria reduction in the first months of treatment with pharmacological or dietary intervention correlates with the degree of long-term (3 to 4 years) renal or cardiovascular protection. Despite the various available treatments to decrease urinary albumin excretion, residual albuminuria persists in many patients. The high residual albuminuria in a proportion of patients is at least in part explained by suboptimal response to the current treatments (i.e., ACE inhibitor or Angiotensin Receptor Blockers).
Dapagliflozin is a sodium-glucose transport inhibitor and inhibits the reabsorption of glucose in the proximal tubule. This leads to a decrease in fasting plasma glucose and HbA1c in patients with type 2 diabetes. In addition, dapagliflozin administration causes a decrease in blood pressure and body weight and an increase in hematocrit suggestive of a diuretic effect. Previous studies have also demonstrated the albuminuria lowering effects of dapagliflozin in patients with type 2 diabetes mellitus.
Although dapagliflozin markedly slows progression of kidney function decline (and reduces cardiovascular outcomes) on a population level, randomized parallel group trials have suggested a marked variation in the response to dapagliflozin between individual patients. By design, randomized parallel group placebo-controlled clinical trials test the efficacy of new interventions on a population level but do not assess the efficacy of a drug for the individual. Although there is variation in response between patients, parallel group trial does not allow conclusions whether this variation is a true variation in drug response, or measurement or temporal random variation. The investigators therefore propose a cross-over trial with repeated administration (i.e., a series of N=1 trials) to ascertain the individual drug response. This design specifically allows for assessment of drug efficacy and safety at an individual level.
Objectives:
- Primary: To determine the individual response to the SGTL2 inhibitor dapagliflozin in urine albumin-to-creatinine ratio (UACR)
- Secondary: To determine the individual response to the SGLT2 inhibitor dapagliflozin in: systolic blood pressure, body weight, eGFR, fasting plasma glucose
Study design:
Randomized placebo-controlled double-blind cross-over N=1 trial. Eligible participants will be invited for screening. After a screening visit, eligible patients will be randomly assigned to a cross-over study consisting of two periods of 1-week treatment with dapagliflozin and two periods of 1-week treatment with placebo in random order with a 1-week wash-out period between every treatment period to avoid cross-over effects. Based on a prior study where patients were exposed to dapagliflozin 10 mg, effects of dapagliflozin on UACR, blood pressure, body weight, eGFR and plasma glucose were fully present after 1 week and returned to baseline 4 days after drug discontinuation. Hence, a 1-week treatment followed by 1 week wash-out is considered sufficient to detect treatment effects.
Study population:
Adult male and female patients with UACR >20 mg/g (2.26 mg/mmol) with type 2 diabetes mellitus treated in primary or secondary healthcare. Subjects will be recruited via general practitioner practices and via the outpatient clinic of the Department of Internal Medicine of the Ziekenhuisgroep Twente, Almelo.
Intervention:
Dapagliflozin 10 mg/day
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
The efficacy and safety of dapagliflozin is established in multiple parallel randomized controlled trials involving more than 25,000 patients with type 2 diabetes. Urinary tract infections and genital infections are the most frequently reported side effects. Dapagliflozin reduces body weight unlike sulfonylurea derivatives and insulin.
Participants visit the outpatient clinic at three occasions (i.e., a screening visit, a second visit and end of study visit) and have to record body weight and blood pressure at home and collect blood and urine at home.
Blood pressure and body weight are measured at home by the participants using ambulant devices (Withings BPM Connect and Withings Body+, respectively). Participants measure their blood pressure and body weight once daily on 28 and 40 days in total, respectively. Capillary blood will be sampled at home by participants using a BD Microtainer® Contact-Activated Lancet (once daily on 22 days in total). Blood is collected with the Hem-Col® device, which is designed to collect capillary blood drawn with a finger prick. In order to make patients comfortable with the blood collection procedures, they first collect a capillary blood sample at the study site during the second visit under supervision of trained lab technicians. A venous blood sample will also be taken during the second visit in order to compare the clinical chemistry assessments in capillary blood with those measured in venous blood samples (NL70447.100.19). Participants will be asked to draw blood samples at home by a finger prick and send the samples to the laboratory. Participants will collect first morning void urine samples through the PeeSpot® device (once daily on 40 days in total) which allows for decentralized urine collection in a small tube. The urine tubes and blood samples will be sent by regular mail to the laboratory. No other invasive measurements will be executed.
The advantage of an N=1 study is that efficacy of the intervention is vetted for the actual participant. Dapagliflozin is currently marketed in the Netherlands and recommended in patients with type 2 diabetes mellitus and eGFR>45 mL/min/1.73m2. Patients who show a satisfactory response to dapagliflozin and whose characteristics fulfill the criteria according to which dapagliflozin can be prescribed in clinical practice are offered to receive dapagliflozin after the study. It is expected that the indication for dapagliflozin will be broadened to patients with eGFR 25-45 mL/min/1.73m2 in the near future. If this occurs, these patients can also be treated on-label in practice.
The expected time investment for participants is 20 hours, including measurements at home. Participants receive restitution of travel costs to visit the outpatient clinic for the screening, randomization and end of study visit. Participants receive no priority in treatment of other diseases in the clinic during this study. Participation in this study is on a free-will base. Participants can keep the body weight scale and blood pressure device at the end of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
- Model description
- Randomized placebo-controlled double-blind cross-over trial with repeated administration (i.e., a series of N=1 trials).
| Arm | Type | Receives |
|---|---|---|
| Option 1 (D-D-P-P) | Other | Drug: Dapagliflozin 10mg Tab, Drug: Placebo, Device: Withings BPM Connect, Device: Withings Body+, Diagnostic Test: Hem-Col Capillary Blood Collection Device, Device: MEMS (Medication Electronic Monitoring System) Cap, Behavioral: Questionnaire: participants' perspectives toward remote data collectionWeek 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Placebo Week 8. Wash-out |
| Option 2 (D-P-D-P) | Other | Drug: Dapagliflozin 10mg Tab, Drug: Placebo, Device: Withings BPM Connect, Device: Withings Body+, Diagnostic Test: Hem-Col Capillary Blood Collection Device, Device: MEMS (Medication Electronic Monitoring System) Cap, Behavioral: Questionnaire: participants' perspectives toward remote data collectionWeek 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out |
| Option 3 (D-P-P-D) | Other | Drug: Dapagliflozin 10mg Tab, Drug: Placebo, Device: Withings BPM Connect, Device: Withings Body+, Diagnostic Test: Hem-Col Capillary Blood Collection Device, Device: MEMS (Medication Electronic Monitoring System) Cap, Behavioral: Questionnaire: participants' perspectives toward remote data collectionWeek 1. Dapagliflozin 10 mg/day Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out |
| Option 4 (P-P-D-D) | Other | Drug: Dapagliflozin 10mg Tab, Drug: Placebo, Device: Withings BPM Connect, Device: Withings Body+, Diagnostic Test: Hem-Col Capillary Blood Collection Device, Device: MEMS (Medication Electronic Monitoring System) Cap, Behavioral: Questionnaire: participants' perspectives toward remote data collectionWeek 1. Placebo Week 2. Wash-out Week 3. Placebo Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out |
| Option 5 (P-D-P-D) | Other | Drug: Dapagliflozin 10mg Tab, Drug: Placebo, Device: Withings BPM Connect, Device: Withings Body+, Diagnostic Test: Hem-Col Capillary Blood Collection Device, Device: MEMS (Medication Electronic Monitoring System) Cap, Behavioral: Questionnaire: participants' perspectives toward remote data collectionWeek 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Placebo Week 6. Wash-out Week 7. Dapagliflozin 10 mg/day Week 8. Wash-out |
| Option 6 (P-D-D-P) | Other | Drug: Dapagliflozin 10mg Tab, Drug: Placebo, Device: Withings BPM Connect, Device: Withings Body+, Diagnostic Test: Hem-Col Capillary Blood Collection Device, Device: MEMS (Medication Electronic Monitoring System) Cap, Behavioral: Questionnaire: participants' perspectives toward remote data collectionWeek 1. Placebo Week 2. Wash-out Week 3. Dapagliflozin 10 mg/day Week 4. Wash-out Week 5. Dapagliflozin 10 mg/day Week 6. Wash-out Week 7. Placebo Week 8. Wash-out |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥18 years
- Diagnosis of type 2 diabetes mellitus
- Urinary albumin-to-creatinine ratio >20 mg/g (2.26 mg/mmol)
- eGFR >30 ml/min/1.73m2
- Willing to sign informed consent
Key exclusion criteria (24 listed)
- Diagnosis of type 1 diabetes
- Prior treatment with SGLT2 inhibitor in the four weeks prior to randomization
- History of severe hypersensitivity or contraindications to dapagliflozin
- Unable to monitor blood pressure / body weight or handle digital technologies
- History of non-adherence to medical regimens or unwillingness to comply with the study protocol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dapagliflozin 10mg TabAlso: Forxiga, (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, A10BK01Oral administration | Drug | Option 1 (D-D-P-P), Option 2 (D-P-D-P), Option 3 (D-P-P-D), Option 4 (P-P-D-D), Option 5 (P-D-P-D), Option 6 (P-D-D-P) |
| PlaceboOral administration | Drug | Option 1 (D-D-P-P), Option 2 (D-P-D-P), Option 3 (D-P-P-D), Option 4 (P-P-D-D), Option 5 (P-D-P-D), Option 6 (P-D-D-P) |
| Withings BPM ConnectCE marked and clinically validated blood pressure monitor. Clinical trial results are within the margin of acceptance defined by the internationally recognized evaluation standard of blood pressure monitors ANSI/AAMI/ISO 81060-2:2013, EN ISO 81060-2:2014, developed by the European Society of Hypertension, British Hypertension Society and Association for the Advancement of Medical Instrumentation/American Heart Association. Blood pressure will be measured by the participants once daily on 28 days. Three consecutive measurements are taken. | Device | Option 1 (D-D-P-P), Option 2 (D-P-D-P), Option 3 (D-P-P-D), Option 4 (P-P-D-D), Option 5 (P-D-P-D), Option 6 (P-D-D-P) |
| Withings Body+CE marked and clinically validated advanced Wi-Fi smart scale. Body weight will be measured by the participants once daily on 40 days. | Device | Option 1 (D-D-P-P), Option 2 (D-P-D-P), Option 3 (D-P-P-D), Option 4 (P-P-D-D), Option 5 (P-D-P-D), Option 6 (P-D-D-P) |
| Hem-Col Capillary Blood Collection DeviceCapillary blood samples will be obtained using a BD Microtainer® Contact-Activated Lancet (Franklin Lakes, New Jersey, USA) once daily on 22 days. These blood samples will be collected into Hem-Col® tubes (Hem-Col, Labonovum, Limmen, the Netherlands), specifically designed for collection of capillary blood acquired through a finger prick. The Hem-Col microtube is equipped with an anticoagulant and a preservation buffer, enhancing the stability of analytes in whole blood. These Hem-Col tubes have the dimensions of standard blood collection tubes and are constructed from polyethylene, featuring a pierceable cap made of thermoplastic elastomers. Each tube incorporates a liquid barrier, with the inner part preventing the loss of Hem-Col preservation fluid and the outer part serving as a scoop for collecting blood from a finger prick. The Hem-Col lithium heparin tubes will be utilized for the analysis of creatinine, CRP, lipid profile, HbA1c, uric acid, glucose and NT-proBNP. | Diagnostic test | Option 1 (D-D-P-P), Option 2 (D-P-D-P), Option 3 (D-P-P-D), Option 4 (P-P-D-D), Option 5 (P-D-P-D), Option 6 (P-D-D-P) |
| MEMS (Medication Electronic Monitoring System) CapMedication will be provided in standard medicine bottles with the MEMS® (Medication Electronic Monitoring System) Cap (AARDEX Ltd, Union City, CA, USA), which is a customizable medication package which records and stores up to 4,000 dosing events. The cap fits on standard medicine bottles and with integrated microcircuits, the child-resistant MEMS® Cap records the date and time whenever a patient opens a vial. The stored information can be transferred at any time through the MEMS® Reader to the adherence software for immediate analysis and interpretation. | Device | Option 1 (D-D-P-P), Option 2 (D-P-D-P), Option 3 (D-P-P-D), Option 4 (P-P-D-D), Option 5 (P-D-P-D), Option 6 (P-D-D-P) |
| Questionnaire: participants' perspectives toward remote data collectionSelf-made questionnaires consisting of 6 multiple choice questions and 2 open questions will be used to assess patient experience and satisfaction to guide and inform future trials and use in clinical practice. | Behavioural | Option 1 (D-D-P-P), Option 2 (D-P-D-P), Option 3 (D-P-P-D), Option 4 (P-P-D-D), Option 5 (P-D-P-D), Option 6 (P-D-D-P) |
Primary outcome
UACR response
Time frame: Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.
The individual response to the SGLT2 inhibitor dapagliflozin in urine albumin-to-creatinine ratio (UACR)
4 secondary outcomes
Systolic blood pressure response
Time frame: Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.
Body weight response
Time frame: Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.
eGFR response
Time frame: Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.
Fasting plasma glucose response
Time frame: Will be assessed within 6 months and reported within 2 years after conclusion of the study.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2024.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dapagliflozin 10mg Tab, Withings BPM Connect and Withings Body+ in people with Diabetes Mellitus, Type 2 and Diabetes Mellitus Type 2 With Proteinuria, run by University Medical Center Groningen at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
UACR response (time frame: Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2024.