Ignite Creation Date:
2024-05-06 @ 8:25 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06374043
Status:
COMPLETED
Last Update Posted:
2024-04-22
First Post:
2024-04-15
Brief Title:
Decentralized N1 Study A Feasible Approach to Evaluate Individual Therapy Response to Dapagliflozin
Sponsor:
University Medical Center Groningen
Organization:
University Medical Center Groningen
Study Overview
Official Title:
Individual Albuminuria Lowering Response to Dapagliflozin in a Decentralized Clinical Trial in Patients With Type 2 Diabetes Mellitus and Elevated Albuminuria
Status:
COMPLETED
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HOME
Brief Summary:
Randomized placebo-controlled double-blind cross-over N1 trial in adult male and female patients with UACR 20 mgg 226 mgmmol 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 mgday 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
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 mgday 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 ie 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 ie a series of N1 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 N1 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 mgg 226 mgmmol 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 mgday
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 25000 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 ie 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 NL7044710019 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 N1 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 eGFR45 mLmin173m2 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 mLmin173m2 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
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 ie 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 ie a series of N1 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 N1 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 mgg 226 mgmmol 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 mgday
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 25000 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 ie 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 NL7044710019 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 N1 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 eGFR45 mLmin173m2 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 mLmin173m2 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
True
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None