Clinical trial NCT02531776: Patient Experiences With Injection Needles
Official title: Patient Experiences With Injection Needles
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Keywords: Diabetes
Needle
Pen needle
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2015-08-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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?

Eligibility criteria: Inclusion Criteria:

Participation in the study is possible if you

* Are a man or woman with type 2 diabetes. An equal distribution of men and women is sought to compare findings between the sexes.
* Take daily injection(s) of anti-diabetic medicine (insulin or glucagon-like-peptide-1 (GLP-1) analogues) with a pen or syringe, and have done so for more than 6 months.
* Are 18-70 years (both included)
* Are slightly overweight, i.e. BMI 25-35 kg/m2.
* Are inactive for at least 6 hours before the study, i.e. transport to the investigation must be carried out without significant physical activity.
* Are Caucasian. Inclusion of other ethnicities can increase data variation and a darker skin tone can make it difficult to read any skin reactions.
* Have no significant body hair on the abdomen (can be shaved away, and if so, this should be done at least 48 hours before the test day)

Exclusion Criteria:

Participation in the study is not possible if one or more of the following criteria are met:

* Known or suspected hypersensitivity to needles, including the needle's lubricant (typically silicon oil), pen / ink color, or other materials that come into contact with the injection site
* Previous participation in the trial
* Intake of medical product which may influence pain perception within the last 14 days before trial
* Insulin pump user
* Previous surgery in the abdominal wall
* Intake of any painkillers within the last week before the test (low-dose aspirin in cardiovascular prophylactic doses is allowed)
* Known active or inactive skin diseases in the abdominal area that may influence pain perception or blood perfusion
* Anticoagulant therapy within the last month (low-dose aspirin in cardiovascular prophylactic doses is authorized, except on test day)
* Pregnant or breastfeeding
* Consumption of alcohol within the last 24 hours before the test
* Intake of drugs within the last 48 hours before the experiment
* Smokers and ex-smokers who use nicotine products (allowed if not used within the past 6 months prior to study entry)
* Moderate to severe lipodystrophy
* Severe neuropathy (grade 0/8, 1/8 or 2/8). This is examined with a Rydell-Seiffer tuning fork.

Primary outcomes:
measure: Pain on 0-100 mm VAS
timeFrame: Immediately after needle insertion.
measure: Area under curve (AUC) of skin blood perfusion increase
timeFrame: Change from baseline (before insertion) to after insertion with continuous measurements for 15 minutes.
Secondary outcomes:
measure: Needle peak penetration force [N] through human skin
timeFrame: At time of needle insertion
measure: Skin reactions (bleeding, bruising, redness, swelling) on a scale from 0 to 4.
timeFrame: 0.5-1 hour after insertion and 20-24 hours after insertion
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: University of Copenhagen
Study officials:
affiliation: University of Copenhagen
name: Kezia A Præstmark, M.Sc.
role: PRINCIPAL_INVESTIGATOR
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