The Reduced Insulinotropic Effect of a Continuous Infusion Relative to a Bolus Injection of GIP

NCT ID: NCT02673554

Last Updated: 2016-02-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31

Brief Summary

In patients with type 2 diabetes, the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) has lost its insulinotropic activity, but more so after continuous versus bolus administration. The design was a two-way crossover design comparing repeated bolus injection and continuous infusion of GIP under hyperglycaemic clamp conditions. Patients were age- gender- and weight-matched with type 2 diabetes, first degree relatives of such patients, and healthy subjects. Investigators performed a:

1. Oral glucose challenge;

2. hyperglycemic clamp (8.5 mmol/l) with two repeated GIP bolus administrations (50 pmol/kg body weight at 30 and 120 min); and

3. hyperglycemic clamp with continuous administration of GIP (2 pmol.kg-1.min-1 from 30-180 min).

To answer the question, whether rapid tachyphylaxis occurs with regard to the insulinotropic action of GIP, investigators studied type 2-diabetic patients, their first-degree relatives, and healthy controls under hyperglycaemic clamp conditions with two GIP bolus injections 90 min apart, and compared this to a continued intravenous infusion of GIP.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oral glucose tolerance test

An oral glucose challenge (75 g)

Group Type: EXPERIMENTAL

Oral glucose tolerance test (OGTT)

Intervention Type: PROCEDURE

an oral glucose challenge (75 g)

GIP Bolus

Hyperglycemic clamp (capillary venous glucose concentration \~ 8.5 mmol/l) with two repeated intravenous bolus injections of synthetic human GIP (50 pmol/kg body weight) administered 30 and 120 min after commencing the hyperglycemic clamp

Group Type: ACTIVE_COMPARATOR

GIP Bolus

Intervention Type: DRUG

bolus injections of synthetic human GIP (50 pmol/kg body weight) administered 30 and 120 min after commencing the hyperglycemic clamp

hyperglycemic clamp

Intervention Type: PROCEDURE

a hyperglycemic clamp (capillary venous glucose concentration \~ 8.5 mmol/l)

GIP Infusion

Hyperglycemic clamp with the continuous intravenous infusion of 2 pmol.kg-1.min-1 synthetic human GIP between 30 and 180 min

Group Type: ACTIVE_COMPARATOR

GIP Clamp

Intervention Type: DRUG

hyperglycemic clamp with the continuous intravenous infusion of 2 pmol.kg-1.min-1 synthetic human GIP between 30 and 180 min

hyperglycemic clamp

Intervention Type: PROCEDURE

a hyperglycemic clamp (capillary venous glucose concentration \~ 8.5 mmol/l)

Interventions

GIP Bolus

bolus injections of synthetic human GIP (50 pmol/kg body weight) administered 30 and 120 min after commencing the hyperglycemic clamp

Intervention Type: DRUG

GIP Clamp

hyperglycemic clamp with the continuous intravenous infusion of 2 pmol.kg-1.min-1 synthetic human GIP between 30 and 180 min

Intervention Type: DRUG

Oral glucose tolerance test (OGTT)

an oral glucose challenge (75 g)

Intervention Type: PROCEDURE

hyperglycemic clamp

a hyperglycemic clamp (capillary venous glucose concentration \~ 8.5 mmol/l)

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Exclusion of pregnancy
• Exclusion of impaired glucose tolerance or type 2 diabetes in metabolical healthy subjects
• current diagnosis of type 2 diabetes according to the guidelines of the German Diabetes Association (DDG) ( Kerner et al . 2001) in subjects of diabetes group
• fasting glucose ≤ 150 mg/dl
• Body-mass-index ≥ 20 kg/m²
• Written consent

Exclusion Criteria

• Type 1 diabetes
• Impaired glucose tolerance or Type 2 diabetes in metabolical healthy subjects
• Ketone bodies urine diagnostics at least ++
• Acidosis
• Fasting blood glucose > 150 mg/dl
• Body-mass-index < 20 kg/m²
• No written consent
• Pregnancy or unsafe contraception in women before menopause
• Active malignancy
• Angina as current, unsolved clinical problem
• Inadequately treated or untreated arterial hypertension ( > 160 mmHg systolic and / or > 95 mmHg diastolic )
• Infection / fever > 37.5 ° C
• Treatment with glucocorticoids
• Insulin therapy within the last three months
• Anemia with a hemoglobin level < 12 g/dl
• Liver function limitations
• Renal impairment ( serum creatinine > 1.5 mg/dl )
• Alcohol or drug abuse
• Participation in clinical trials in the last 3 months
• Inability or unwillingness to comply with the requirements of the Protocol
• Known hypersensitivity to GIP

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Diabeteszentrum Bad Lauterberg im Harz

OTHER

Sponsor Role: lead

Responsible Party

Michael A. Nauck

Prof. Dr. med. Michael A. Nauck

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael A. Nauck, Prof.

Role: PRINCIPAL_INVESTIGATOR

Diabeteszentrum Bad Lauterberg

Other Identifiers

GIP and Tachyphylaxis

Identifier Type: -

Identifier Source: org_study_id