Environmental Effects Type 1 Diabetes Mellitus
Condition: Type1diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      Type 1 Diabetes mellitus (T1D) is characterized by βcell destruction and a long life
      requirement of exogenous insulin. The bolus basal insulin regimen is a widely accepted
      therapy concept to treat hyperglycaemia in patients with T1D. This concept requires a very
      good knowledge of the individuals prandial and basal insulin requirements. However, insulin
      requirement depends on insulin absorption from the injection site and the individual's
      insulin sensitivity which relies on a number of effects including body composition,
      inflammatory processes and environmental factors. Climatic factors such as differences in air
      temperature could affect both, insulin absorption and insulin sensitivity as suggested by
      recent reports. For instance, it is reported that hot baths can accelerate the absorption of
      short acting but not of long acting insulin formulations from the subcutaneous depot. In
      addition, local warming of the injection site by a novel device (InsuPatch) results as well
      in an accelerated insulin action profile of short acting insulins. Moreover, Berglund et al.
      reported seasonal variations in insulin sensitivity in elderly men with increased insulin
      sensitivity during summer time.

      Although an effect of temperature on insulin absorption and action can be assumed and was
      subject to current clinical trials, there is only little knowledge on the effect of humidity
      and the cumulative effect of humidity and temperature on insulin pharmacodynamics and
      pharmacokinetics. For subjects with type 2 diabetes it was reported that accommodation to
      high temperatures and moist air of more than 75% is impaired compared to healthy subjects as
      determined by skin blood flow, temperature and moisture. Although it can be estimated that
      changes in blood flow due to hot and moist air affect the pharmacokinetics and
      pharmacodynamics of subcutaneous prandial insulins, to our knowledge no such study in
      subjects with T1D using the euglycaemic clamp technique was carried out yet. In order to
      assess the effect of temperature and humidity on insulin action, subjects with type 1
      diabetes will be administered a single dose of short acting insulin in an environmental
      chamber either at 15°C or a warm environment of 40°C with either a low or high humidity (10%
      vs. 90%). Moreover, an exploratory part of the trial will evaluate the measurement
      performance of several blood glucose meters under the experimental climatic situations.
    

Detailed description: 
      BACKGROUND Type 1 Diabetes mellitus (T1DM) is characterised by β-cell destruction and a
      lifelong requirement of exogenous insulin. The basal-bolus insulin regimen is widely accepted
      therapy to treat hyperglycaemia in patients with T1DM. This concept requires a very good
      knowledge of the individual's prandial and basal insulin requirements. However, insulin
      requirement depends on insulin absorption from the injection site and the individual's
      insulin sensitivity that relies on a number of factors including body composition,
      inflammatory processes and environmental factors. Environmental factors such as differences
      in air temperature could affect both, insulin absorption and insulin sensitivity as suggested
      by recent reports. For instance, it is reported that hot baths can accelerate the absorption
      of short-acting but not of long-acting insulin formulations from the subcutaneous depot. In
      addition, local warming of the injection site by a novel device (InsuPatch) results in an
      accelerated insulin-action profile of short-acting insulins. Moreover, Berglund et al.
      reported seasonal variations in insulin sensitivity in elderly men with increased insulin
      sensitivity during summer time.

      Although an effect of temperature on insulin absorption and action can be assumed, there is
      only little knowledge on the effect of humidity and the cumulative effect of humidity and
      temperature on insulin pharmacodynamics and pharmacokinetics. For subjects with type 2
      diabetes it was reported that accommodation to high temperatures and moist air of more than
      75% is impaired compared to healthy subjects as determined by skin blood flow, temperature
      and moisture.

      Although it can be estimated that changes in blood flow due to hot and moist air affect the
      pharmacokinetics and pharmacodynamics of subcutaneous prandial insulins, to our knowledge no
      such study in subjects with T1D using the euglycaemic clamp technique has been performed. In
      order to assess the effect of temperature and humidity on insulin action, subjects with type
      1 diabetes will be given a single dose of short-acting insulin in an environmental chamber
      either at 15°C or a warm environment of 30°C with either a low or high humidity (10% vs.
      60%).

      TRIAL OBJECTIVES The objective of this trial is to assess the effect of different
      temperatures and humidity levels on the pharmacokinetic and pharmacodynamic profiles of
      short-acting insulin in subjects with type 1 diabetes mellitus.

      TRIAL DESIGN The trial will be a single-centre, open label, 3-way cross-over, euglycaemic
      glucose clamp trial in subjects with type 1 diabetes mellitus. The pharmacodynamic and
      pharmacokinetic properties of insulin Humalog dosed at 0.2 U/kg will be investigated.

      ENVIRONMENTAL SETTINGS

        -  15 °C and 10% humidity

        -  30 °C and 10% humidity

        -  30 °C and 60% humidity

      ASSESSMENTS

        -  6 visits to the clinical unit: informed consent and screening visit (Visit 1, within 28
           days prior to Visit 2a), Pre-dosing visit (Visit 2a, within 3 days of 2b), 3 dosing
           visits (Visit 2b, 3 & 4, wash-out period of 3-21 days between each visit), and 1
           follow-up (FUP) examination (Visit 5, 3-14 days after last dosing visit)

        -  Change in insulin regimen (72 hours prior to each dosing):

      The patients will be switched from Insulin Lantus or detemir to NPH 48 hours before dosing
      visit. The NPH insulin will then be stopped 22 hours before dosing visit except short acting
      insulin which will be stopped 6-8 hours before visit.

        -  Euglycaemic clamp setting for 6 hours after administration on dosing Visits 2b, 3 & 4

        -  Blood to be collected for the determination of PK insulin concentrations on Visit 2b, 3
           & 4 before and after administration of insulin

        -  Blood glucose will be continuously monitored pre-administration and for 6 hours after
           administration of insulin

        -  Determination of skin blood flow via Laser-Doppler

        -  Standard safety parameters will be assessed throughout the study.
    

Intervention name(s): Humalog
Intervention type(s): Drug
Intervention description(s): Subcutaneous injection of Humalog and assessing Pharmacokinetics and Pharmacodynamics properties of Humalog under different environmental conditions
Other intervention name(s): Insulin lispro
Intervention MeSH terms: Insulin Lispro
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science