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Study to Estimate the Effects of Inhaled Versus Intravenous (IV) Infusion of Human Insulin in Subjects With Type 1 Diabetes

15 février 2008 mis à jour par: University of Pittsburgh

Open-Label Randomized Two-Way Crossover Pilot Study to Estimate the Effects of Inhaled vs. IV Infusion of Human Insulin With Regards to Glucose Disposal in Subjects With Type 1 Diabetes Mellitus

University of Pittsburgh Medical Center (UPMC) diabetes research physicians are studying the action in muscle tissue of "inhaled" insulin (Exubera®) and "infused" (intravenous or IV) insulin on blood sugar control in people with type 1 diabetes. Type 1 diabetics often take 2-4 shots of insulin every day. Exubera may offer an alternative to these insulin injections.

Aperçu de l'étude

Statut

Complété

Les conditions

Diabète sucré de type 1

Intervention / Traitement

Médicament: Exubera

Description détaillée

A dry powder insulin formulation delivered by an aerosol inhaler has been in clinical development for use in types 1 and 2 diabetes mellitus (DM) and just recently (1-27-06) received approval from the U.S. Food and Drug Administration (FDA) for the clinical treatment of diabetes. Administration of insulin without the need for subcutaneous (SC) injection is an attractive alternative for patients with diabetes. There are preclinical and clinical data that indicate inhalation of insulin results in a more potent effect on glucose disposal and a lower fasting glucose than is attained with equivalent dosing of SC or intravenous (IV) insulin. The physiological mechanism(s) are unclear, but occur even when matched for pharmacokinetics.

The current proposal seeks primarily to more fully delineate whether there are physiological differences in the metabolic effects of inhaled compared to IV infused insulin, giving IV insulin to match the pharmacokinetics (PK) achieved with inhaled insulin.

There are 3 specific aims:

The first aim is to establish a protocol for matching the PK of inhaled insulin with the PK of intravenously infused insulin. An infusion algorithm has been developed and will be tested and refined in healthy volunteers (n = 3-5), and will be used for the physiological studies (aims) outlined below.
The second aim is to perform Positron Emission Tomography (PET) imaging of [18F]-FDG uptake by muscle, following administration of a single dose of inhaled compared to infused insulin. Volunteers with type 1 DM (n =12) will be studied, serving as his/her within-subject control, under each condition of insulin administration.
In these type 1 diabetes mellitus (type 1 DM) volunteers, we will test the hypothesis that a single dose of inhaled versus infused insulin, matched for arterial concentrations, causes greater stimulation of muscle glucose uptake.
The third aim is to determine overnight rates of glucose production and plasma glucose after a single pre-dinner dose of inhaled compared to IV infused insulin. The same 12 volunteers studied for Aim 2 will be studied the evening preceding the PET imaging studies and will serve as his/her within-subject control, under each condition of insulin administration.

Type d'étude

Interventionnel

Inscription (Anticipé)

Phase

Phase 4

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

États-Unis
- Pennsylvania
  - Pittsburgh, Pennsylvania, États-Unis, 15213
    - University of Pittsburgh

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 50 ans (Adulte)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

Ages 18 to 50 years old
Body mass index (BMI) 20 to 27 kg/m2 and a total body weight > 50 kg (110 lbs)
Blood pressure: systolic < 150; diastolic < 95.
Type 1 DM
Have diagnosed diabetes type 1 for a minimum of 12 months prior to study entry
In good general health with no evidence or history of clinically significant hematological, renal, endocrine (other than diabetes), pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
Hematocrit (Hct) > 34%
ALT < 60; AST < 60
Alkaline phosphatase (Alk Phos) < 150
Sensitive thyroid-stimulating hormone (sTSH) < 6
Fasting (morning) glucose 100-160 mg/dl
Documented hemoglobin A1c (HbA1c) < 7.5% at time of entry
Triglycerides < 175
Cholesterol < 275

Exclusion Criteria:

Exclude if unable to master use of the inhalation device after 3 attempts
Exclude if positive urine drug screen
Exclude if any episodes of severe hypoglycemia in the past 3 months
Exclude if pregnant or breastfeeding or unwilling to use an acceptable method of non-hormonal contraception from at least 14 days prior to the first dose of Exubera® until study is completed.
Exclude if any history of (h/o) asthma or chronic obstructive pulmonary disease (COPD)
Exclude if forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) < 70% predicted
Exclude if treatment with an investigational drug within 30 days preceding the first dose of trial medication.
Exclude if blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing
Exclude if unable or unwilling to comply with the protocol as written
Exclude if any use of tobacco or nicotine containing products within the past 6 months
Exclude if history of regular alcohol consumption exceeding 7 drinks/week for females or 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6 months of screening
Exclude if claustrophobic, any surgical or vascular implants or pacemakers, or any metal in the body

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

Objectif principal: Traitement
Répartition: Randomisé
Modèle interventionnel: Affectation croisée
Masquage: Aucun (étiquette ouverte)

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
To perform positron emission tomography (PET) imaging of [18F]-fluoro-deoxy-glucose (FDG) uptake by muscle, following administration of a single dose of inhaled compared to infused insulin in volunteers with type 1 diabetes

Mesures de résultats secondaires

Mesure des résultats
To determine overnight rates of glucose production and plasma glucose after a single pre-dinner dose of inhaled compared to IV infused insulin in volunteers with type 1 diabetes

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

University of Pittsburgh

Collaborateurs

Pfizer

Les enquêteurs

Chercheur principal: David E. Kelley, MD, University of Pittsburgh

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 avril 2006

Achèvement de l'étude (Réel)

1 décembre 2006

Dates d'inscription aux études

Première soumission

17 avril 2006

Première soumission répondant aux critères de contrôle qualité