DPP-4 Inhibitor and Serum BNP Level of Diabetic Patients With Congestive Heart Failure

Investigation of the Impact of Dipeptidyl Peptidase-4 (DPP-4) Inhibition on Serum B-type Natriuretic Peptide (BNP) Level of Diabetic Patients With Congestive Heart Failure.

We thought to investigate the influence of DPP-4 inhibitor on the serum BNP level of diabetic patients with congestive heart failure. This study consists of two protocols. In the first protocol, diabetic patients with high level of serum BNP (100-2000 pg/ml) receiving outpatient treatment with any type of DPP-4 inhibitor at our institution will be enrolled. After baseline data collection, DPP-4 inhibitor will be suspended for one month and serum BNP will be measured. The DPP-4 inhibitor will be resumed and after another month, serum BNP will be measured again. In the other protocol, diabetic patients who were hospitalized due to heart failure were enrolled. DPP-4 inhibitor will be started (if the patient is not taking a DPP-4 inhibitor) or suspended (if the patient is taking a DPP-4 inhibitor) after stabilization of heart failure, and serum BNP will be measured before and after the drug administration or suspension.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Diabetes Mellitus
• Intervention / Treatment: Drug: Suspending DPP-4 inhibitor, in outpatient service; Drug: Starting DPP-4 inhibitor after treatment of heart failure; Drug: Suspending DPP-4 inhibitor after treatment of heart failure

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Taito-ku, Tokyo, Japan
      • Mitsui Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Outpatient arm

Inclusion Criteria:

• Type 2 diabetes patient with congestive heart failure under treatment with DPP-4 inhibitor (sitagliptin, vildagliptin, alogliptin, linagliptin, teneligliptin, anagliptin or saxagliptin) .
• High serum BNP (100-2000pg/ml).
• Patients who have given informed consent to participation in the study.

Exclusion Criteria:

• HbA1c over 9.0%.
• Patients who changed medication within 1 months before inclusion.
• Judged as ineligible by clinical investigators.

Hospitalization arm

Inclusion Criteria:

• Type 2 diabetes patient who were hospitalized for congestive heart failure.
• Patients who have given informed consent to participation in the study.

Exclusion Criteria:

• Patients on insulin therapy.
• Judged as ineligible by clinical investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Outpatient arm; After baseline data collection, DPP-4 inhibitor will be suspended for one month and serum BNP will be measured. The DPP-4 inhibitor will be resumed and after another month, serum BNP will be measured again.	Drug: Suspending DPP-4 inhibitor, in outpatient service; After baseline data collection, DPP-4 inhibitor (sitagliptin, vildagliptin, alogliptin, linagliptin, teneligliptin, anagliptin or saxagliptin) will be suspended for one month and serum BNP will be measured. The DPP-4 inhibitor will be resumed and after another month, serum BNP will be measured again.
Experimental: Hospitalization arm 1; After hospitalization, medication for diabetes will be suspended. During the treatment for heart failure, drugs other than DPP-4 inhibitor will be resumed when required. After the stabilization of heart failure, DPP-4 inhibitor will be resumed (or administered if it was not prescribed before hospitalization) and serum BNP before and after the initiation of DPP-4 inhibitor will be measured.	Drug: Starting DPP-4 inhibitor after treatment of heart failure; After hospitalization, medication for diabetes will be suspended. During the treatment for heart failure, drugs other than DPP-4 inhibitor will be resumed when required. After the stabilization of heart failure, DPP-4 inhibitor will be resumed (or administered if it was not prescribed before hospitalization) and serum BNP before and after the initiation of DPP-4 inhibitor will be measured.
Experimental: Hospitalization arm 2; After hospitalization, medication for diabetes may be suspended or continued. During the treatment for heart failure, drugs including DPP-4 inhibitor will be resumed when required. After the stabilization of heart failure, DPP-4 inhibitor will be suspended and serum BNP before and after the suspension of DPP-4 inhibitor will be measured.	Drug: Suspending DPP-4 inhibitor after treatment of heart failure; After hospitalization, medication for diabetes may be suspended or continued. During the treatment for heart failure, drugs including DPP-4 inhibitor will be resumed when required. After the stabilization of heart failure, DPP-4 inhibitor will be suspended and serum BNP before and after the suspension of DPP-4 inhibitor will be measured.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum BNP level with and without DPP-4 inhibitor use.	In the outpatient arm, changes in serum BNP level measured 1 month after suspension of DPP-4 inhibitor, and 1month after resumption of the DPP-4 inhibitor will be analyzed. In the hospitalization arm, serum BNP before and 2-3 days after the initiation of DPP-4 inhibitor will be measured and compared.	3 days to 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All cause mortality	Any deaths during the study period. (only for the outpatient arm)	2 months
Cardiovascular death	Any cardiovascular deaths during the study period. (only for the outpatient arm)	2 months
Heart failure hospitalization	Any hospitalization due to worsening of heart failure during suspension of or within 1month after resumption of taking a DPP-4 inhibitor. (only for the outpatient arm)	2 months
Worsening heart failure	Worsening of heart failure after the initiation of DPP-4 inhibitor. (only for the hospitalization arm)	3 days
Echocardiographic measures (Changes in echocardiographic measures during the study period.)		3 days to 2 months
Other neurohormonal factors (Changes in plasma renin, aldosterone, serum stromal cell-derived factor 1 alpha, serum active glucagon-like peptide-1, serum active glucose-dependent insulinotropic polypeptid)	Changes in plasma renin, aldosterone, serum stromal cell-derived factor 1 alpha, serum active glucagon-like peptide-1, serum active glucose-dependent insulinotropic polypeptide during the study period.	3 days to 2 months

Collaborators and Investigators

• Sponsor: Mitsui Memorial Hospital
• Collaborators: Mitsukoshi Health and Welfare Foundation
• Investigators: Principal Investigator: Akihiro Isogawa, M.D., Mitusui Memorial Hospital, Division of diabetes

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: November 30, 2014
• First Submitted That Met QC Criteria: December 6, 2014
• First Posted (Estimate): December 9, 2014

Study Record Updates

• Last Update Posted (Actual): March 22, 2018
• Last Update Submitted That Met QC Criteria: March 20, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Dipeptidyl-Peptidase IV Inhibitors
• Other Study ID Numbers: MMHMEC2014-10