Patient Experiences With Injection Needles
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      This study will focus on how different injection needles are perceived by patients. The
      needles differ in design and mechanical properties, and will be tested in people with Type 2
      Diabetes. The measured parameters during and after needle insertion are: penetration force
      through skin (measured with force gauge), pain perception (rated on visual analog scale, VAS,
      on a scale from 0 to 10), and skin blood perfusion at insertion site (measured with laser
      speckle contrast scanner). Furthermore, any skin reactions will be recorded.
    

Detailed description: 
      It is estimated that there presently are about 370 million diabetics in the world, and the
      number is increasing, particularly in newly industrialized countries, such as China and
      India. Approximately 90% of diabetics have Type 2 diabetes, often caused by lifestyle, such
      as obesity and lack of exercise. 3-5% of diabetics have Type 1 diabetes, and the cause of the
      disease is unknown. The remaining 5-7% have either pregnancy diabetes (temporary illness),
      MODY ("Maturity-Onset Diabetes of the Young") or rarer forms of diabetes.

      For the treatment of Type 1 diabetes, insulin has to be injected into the subcutaneous tissue
      from which it is taken up into the circulation. People with Type 1 Diabetes do not produce
      insulin and must thus inject insulin to stabilize blood sugar levels, typically via one or
      two daily injections with basal insulin, as well as so-called "bolus" injections at the time
      of each meal. This adds up to approximately 4-5 daily insulin injections. Type 2 diabetics,
      who are still "early" in the disease, have reduced sensitivity to the insulin they produce,
      so the pancreas overproduces insulin. Beyond lifestyle changes, treatment with metformin in
      tablet form will in this case be the first-line drug. In the later stages of the disease, the
      insulin production decreases and insulin therapy should be initiated, optionally in
      combination with a GLP-1 analogue (Glucagon-Like Peptide-1). It is estimated that only half
      of all people with Type 2 diabetes are diagnosed, and that half of those diagnosed are not in
      treatment. Worldwide, about 27% of the treated type 2 diabetic patients receive insulin
      treatment, or a GLP-1 analog, 1-2 times a day.

      From the above figures it can be estimated that over 100 million diabetes injections are
      performed globally every day. In addition, other disorders also require subcutaneous
      administration of drugs, e.g. growth hormone therapy or inflammatory diseases such as
      rheumatoid arthritis or intestinal diseases. Thus, it is of great importance that the needles
      used for injections, are as painless and comfortable to use as possible.

      The larger needle manufacturers have for many years sought to make needles less painful and
      to cause less skin trauma. Until recently, these measures have primarily been making needles
      thinner and shorter, but now needles with alternative grindings and needle tip designs are
      marketed. This is to compensate for the decreased robustness of the new very thin needles,
      which increase the risk of the patients damaging the needle tip during an injection. Little
      is known, however, of how these design changes influence the perception of pain, skin damage,
      etc.

      Despite the large market for subcutaneous needles, the methods to test newly developed
      needles have remained the same for many years. One of the methods frequently used is a
      mechanical test where the needle is passed through a rubber strip, and the penetration force
      is measured. This method is rapid, reproducible and with very little variation, but there are
      no published data comparing the force measured in the rubber strip, with that measured in
      humans, and how or if the penetration force in a rubber strip relates to pain, discomfort, or
      other physiological parameters. Smith compares the insertion forces measured in the rubber
      strip and in a piece of cut off porcine tissue with the conclusion that these two behave very
      differently and that the rubber strip is estimated to be primarily useful in testing the
      needle lubrication and other friction-reducing parameters.

      The second method often used is a subjective patient assessment, where the test subject uses
      a 'Visual Analogue Scale' (VAS) to indicate how much pain he or she experiences in connection
      with the needle insertion. Pain indicated by VAS is a known and accepted method, but is
      simultaneously a measurement method with great variety, because a person's pain sensitivity
      depends on many things such as stress levels, emotional state, as well as expectations for
      the experience.

      This project is innovative in that it introduces a new method for quantitatively measuring
      small tissue damages in the skin, as for example, a needle insertion.

      The study combines technological and medical research in the form of mechanical design of
      medical devices and biological evaluation of mechanical impact, which in our opinion is
      highly relevant and quite innovative. Results from this study will be used to develop new and
      improved needles, which are predicted to increase patient satisfaction and make everyday life
      with injections easier and more convenient for the many millions of people with diabetes who
      every day take insulin and / or GLP-1 injections .

      The method is based on the Laser Speckle technology, and measures the tissue damage in terms
      of the increased skin blood perfusion in connection with a needle insertion. Prior to this
      project, the project group performed a number of tests on pigs and the method has proven to
      be sensitive enough to detect differences in the blood perfusion that occurs as a result of
      differences in tissue damage caused by insertion of needles that vary less than 0.1 mm in
      diameter, Williams et al used a photoelectric pletysmografi (PPG) to investigate changes in
      skin blood perfusion in human subjects following injections with insulin and diluted insulin,
      as well as with a needle insertion to investigate the effect of the needle trauma alone. A
      rapid increase in blood flow was seen for all interventions. Insulin injections resulted in
      increased signal for more than 60 minutes after the injection, whereas the diluted liquid and
      the needle insertion created an increased signal for about 10 minutes. By using laser Doppler
      technology, Rayman et al studied how the skin circulation changed after needle insertion in
      people with and without diabetes. The study revealed that the people with diabetes had lower
      maximum-perfusion after needle insertion than the healthy subjects. Both of the above
      mentioned clinical studies indicate that the method obtained from the project group's pig
      studies could be transferred to a human study.

      Thus, the study will include 35 test subjects who will receive needle insertions with 18
      differently designed needles. Penetration force through the skin, pain perception and skin
      blood perfusion will be recorded for all needles, and any skin reactions will be recorded. By
      the end of the study, the following questions can be answered:

        1. Which needle design parameters influence pain and skin blood perfusion, and are these
           two effects related?

        2. Does skin blood perfusion after needle insertions in humans compare with those measured
           in pigs?

        3. Does penetration force relate to pain and skin blood perfusion, which needle design
           parameters influence the force in skin, and how does it relate to the penetration force
           in a rubber strip?
    

Intervention name(s): Subcutaneous insertions of needles
Intervention type(s): Device
Intervention description(s): Various types of needles with different designs and mechanical properties.
Five marketed needles are included: NovoFine 28G x 12 mm (Novo Nordisk A/S, Denmark), NovoFine 30G x 6 mm (Novo Nordisk A/S, Denmark), NovoFine 32G tip x 6 mm (Novo Nordisk A/S, Denmark), BD Ultra-Fine 32G x 4 mm Pentapoint (Beckton, Dickinson & Company, USA), and Terumo Nanopass 34G x 5 mm (Terumo, Japan).
Ten needles have been exclusively manufactured for this clinical trial by Hart Needles, USA. These needles vary in diameter, number of needle tip grinding, and angles of grindings.
Three needles have been modified from the original (NovoFine 32G x 6 mm) with lack of lubrication or damaged needle tip for simulations of repeated use.
No drugs are injected. Only the needle insertion is evaluated.
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Diabetes; Needle; Pen needle