Safety Study of Intranasal Insulin in Type 1 Diabetes and Diabetic Peripheral Neuropathy (IIDPN)

Study Description

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Brief Summary:

The aim of this study is to evaluate the safety and tolerability of intranasal insulin in people with type 1 diabetes and diabetic peripheral neuropathy and to determine whether intranasal insulin is effective in slowing the progression of diabetic neuropathy.

Condition or disease	Intervention/treatment	Phase
Diabetic Peripheral Neuropathy	Drug: Novolin Toronto insulin; Drug: Normal saline	Phase 2

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	12 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Prevention
Official Title:	A Phase IIa Dose Escalation Pilot Study to Investigate the Safety and Tolerability of Intranasal Insulin in Subjects With Diabetic Polyneuropathy.
Study Start Date :	August 2011
Actual Primary Completion Date :	July 2012
Actual Study Completion Date :	July 2012

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Novolin Toronto insulin	Drug: Novolin Toronto insulin; Subjects randomized to active drug are provided with 20 IU BID of Novolin Toronto at randomization (week 5). The dosing is prescribed to be taken 30 minutes after the morning meal (breakfast) and 30 minutes after the evening meal (supper). Subjects are asked to consume their meals and take their doses of study treatment within the same time frame each day. Dose escalations occur every 2 weeks with the insulin increasing to 40 IU BID at week 7, then 80 IU BID at week 9. The study completes at week 11. The total treatment period is 6 weeks. The insulin is diluted with an amount of normal saline to provide a total volume in the study treatment vial to equal 1.1 milliliters.
Placebo Comparator: Normal saline	Drug: Normal saline; Subjects randomized to placebo are provided with 1.1 milliliters of normal saline at randomization (week 5). The study completes at week 11. The total treatment period is 6 weeks. The dosing is prescribed to be taken 30 minutes after the morning meal (breakfast)and 30 minutes after the evening meal (supper). Subjects are asked to consume their meals and take their doses of study treatment within the same time frame each day. The amount of normal saline in the study treatment vial (1.1 milliliters) is identical in volume to the active insulin being used in the study .

Outcome Measures

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Primary Outcome Measures :

1. Hypoglycemia monitoring [ Time Frame: 8 weeks ]

   Hypoglycemia is defined by the development of autonomic or neuroglycopenic symptoms, and with or without the presence of a blood glucose measurement.

   All qualifying subjects are provided with blood glucose testing supplies to monitor blood glucoses six times daily from week 3 to week 11 of the study.

   Any severe hypoglycemia or increase of hypoglycemia of greater than 30% from the baseline phase (week 3 to week 5) is deemed clinically significant and is reviewed by the investigator to determine subject continuation with study treatment.

Secondary Outcome Measures :

1. Treatment satisfaction questionnaire for medication (TSQM) [ Time Frame: 6 weeks ]
   The TQSM assesses the overall global impression of the treatment by the study subjects. During the study, the TSQM is administered at weeks 7, 9 and 11.
2. Adverse effects [ Time Frame: 11 weeks ]
   The subject's overall health is assessed throughout the study to determine any changes with respect to existing history, in addition to capturing any new medical conditions that may arise.
3. The UTAH early neuropathy scale [ Time Frame: 6 weeks ]
   The UTAH early neuropathy scale, a standarized physical examination scale, is used to measure changes in sensory neuropathy. During the study, the scale is administered at the time of randomization (week 5), then every 2 weeks until the end of study (week 11).
4. Corneal confocal microscopy [ Time Frame: 6 weeks ]
   The corneal confocal microscopy measures corneal nerve fiber branch length and density. This procedure is done prior to week 5 (randomization) and immediately prior to week 11 (end of study).
5. Electrophysiology [ Time Frame: 6 weeks ]

   The following components will be measured to monitor changes in nerve conduction:

   1. Sural conduction velocity
   2. Radial SNAP amplitude
   3. Radial:Sural SNAP ratio

   The nerve conduction tests are completed prior to week 5 (randomization) and immediately prior to week 11 (end of study).

6. McGill pain questionnaire [ Time Frame: 6 weeks ]
   The McGill pain questionnaire, a standardized scale of rating pain on a scale of 0 (no pain) to 10 (worst pain), is used to monitor change in subject's pain symptoms. During the study, subjects complete this questionnaire at week 5 (randomization) and then every 2 weeks until the end of study (week 11).
7. Short Form-36 (SF-36) Quality of life scale [ Time Frame: 6 weeks ]
   The SF-36 qualify of life scale, a standardized scale, is used to monitor change in subject reported functionality, well being, and overall health status. During the study, subjects complete this questionnaire at week 5 (randomization) and then every 2 weeks until the end of study (week 11).

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Patients classified as having type 1 diabetes mellitus according to the Canadian Diabetes Association Criteria.

• Patients clinically defined as having DPN, meeting at least two of the following conditions:

  1. clinical signs of polyneuropathy;
  2. Symptoms of nerve dysfunction;
  3. Nerve conduction deficits in at least 2 nerves.
• Aged 18 through 70 years (inclusive).
• Body Mass Index (BMI) <30 kilograms/meter2.

Exclusion Criteria:

• Any other possible etiology contributing to the neuropathy:

  1. History of prolonged untreated hypothyroidism.
  2. Presence of untreated B12 deficiency.
  3. Presence of a paraproteinemia, detected using serum protein electrophoresis with a minimal threshold detection of 2 g/L.
  4. Use of a neurotoxic medication with a clear association with peripheral neuropathy within the past 1 year based upon clinical impression of association.
  5. Previous exposure chemotherapeutic agents with a clear association with peripheral neuropathy at any time.
• History of 2 or more severe hypoglycemic episodes within the previous 6 months.
• History of clustering of hypoglycemia episodes within the previous 12 months.
• History of active or recent (<5 years) malignancy.
• History of systemic or local nasal disease that would complicate the use of intranasal insulin.
• Presence of diabetic nephropathy requiring dialysis.
• Presence of active proliferative retinopathy requiring surgery within 6 months.
• Pregnancy or lactation (female subject of reproductive age must be on contraception).

• Active cardiovascular disease:

  1. Recent angina (<5 years)
  2. Recent myocardial infarction (<5 years)
  3. Congestive heart failure
• Active psychiatric disorder or previous history of psychosis.
• Unable to understand or provide consent.
• Previously documented hypersensitivity to insulin.
• History of hypoglycemia unawareness.
• Glycated hemoglobin < 7.0%.
• Ongoing involvement in another investigational drug trial.

Contacts and Locations

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Locations

Canada, Alberta
Heritage Medical Research Clinic
Calgary, Alberta, Canada, T2N 4Z6

Sponsors and Collaborators

University of Calgary

Investigators

Principal Investigator:	Lawrence M Korngut, MD, FRCPC	University of Calgary

More Information

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Responsible Party:	DR. LAWRENCE KORNGUT, Medical Doctor, Neurologist, University of Calgary
ClinicalTrials.gov Identifier:	NCT01469559 History of Changes
Other Study ID Numbers:	UCALG-IIDPN
First Posted:	November 10, 2011
Last Update Posted:	August 10, 2012
Last Verified:	August 2012

Keywords provided by DR. LAWRENCE KORNGUT, University of Calgary:

Insulin; Diabetic neuropathy; Intranasal administration; Pilot project

Additional relevant MeSH terms:

Peripheral Nervous System Diseases; Diabetic Neuropathies; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus	Endocrine System Diseases; Insulin, Globin Zinc; Insulin; Hypoglycemic Agents; Physiological Effects of Drugs