Decentralized N=1 Study: A Feasible Approach to Evaluate Individual Therapy Response to Dapagliflozin.

NCT06374043 | Completed Phase 4 FDA Drug FDA Device

• 1 other identifier: 2020/1002
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus Type 2 With Proteinuria; Diabetes Mellitus; Diabetes; Diabetes Complications; Albuminuria; Chronic Kidney Diseases; Chronic Kidney Disease Due to Type 2 Diabetes Mellitus; CKD; Proteinuria

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; Sodium Glucose Co-Transporter 2

Outcome Measures

Primary Outcomes (1)

• UACR response

  The individual response to the SGLT2 inhibitor dapagliflozin in urine albumin-to-creatinine ratio (UACR)

  Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.

Secondary Outcomes (4)

• Systolic blood pressure response

  Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.

• Body weight response

  Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.

• eGFR response

  Will be assessed within 6 months and reported within 1.5 years after conclusion of the study.

• Fasting plasma glucose response

  Will be assessed within 6 months and reported within 2 years after conclusion of the study.

Study Arms (6)

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

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

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

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

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

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

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

Interventions

Dapagliflozin 10mg Tab DRUG

Oral administration

Also known as: Forxiga, (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, A10BK01

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)

Placebo DRUG

Oral administration

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 Connect DEVICE

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.

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+ DEVICE

CE marked and clinically validated advanced Wi-Fi smart scale. Body weight will be measured by the participants once daily on 40 days.

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 Device DIAGNOSTIC_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.

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) Cap DEVICE

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.

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 collection BEHAVIORAL

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.

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)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• AstraZeneca: collaborator

Study Sites (2)

Ziekenhuisgroep Twente

Almelo, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Diabetes Complications; Albuminuria; Renal Insufficiency, Chronic; Proteinuria

Interventions

dapagliflozin; Micro-Electrical-Mechanical Systems

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Chronic Disease; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Electrical Equipment and Supplies; Equipment and Supplies; Manufactured Materials; Technology, Industry, and Agriculture

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized placebo-controlled double-blind cross-over trial with repeated administration (i.e., a series of N=1 trials).

Study Record Dates

• First Submitted: April 15, 2024
• First Posted: April 18, 2024
• Study Start: May 11, 2021
• Primary Completion: September 13, 2022
• Study Completion: September 13, 2022
• Last Updated: April 22, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share

Locations

NL (2)