Diabetic Peripheral NeuropathyPhase 2IIDPNNCT01469559
Safety Study of Intranasal Insulin in Type 1 Diabetes and Diabetic Peripheral Neuropathy
A Phase 2 study testing Novolin Toronto insulin and Normal saline in people with Diabetic Peripheral Neuropathy, run by University of Calgary at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Diabetic Peripheral Neuropathy
- What is being tested?
- Novolin Toronto insulin and Normal saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2011to Jul 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- clinical signs of polyneuropathy;
- Symptoms of nerve dysfunction;
- Nerve conduction deficits in at least 2 nerves.
- Aged 18 through 70 years (inclusive).
- Body Mass Index (BMI) <30 kilograms/meter2.
Who cannot join
- Any other possible etiology contributing to the neuropathy:
- History of prolonged untreated hypothyroidism.
- Presence of untreated B12 deficiency.
- Presence of a paraproteinemia, detected using serum protein electrophoresis with a minimal threshold detection of 2 g/L.
- Use of a neurotoxic medication with a clear association with peripheral neuropathy within the past 1 year based upon clinical impression of association.
- Previous exposure chemotherapeutic agents with a clear association with peripheral neuropathy at any time.
Show all 23Show fewer
- 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:
- Recent angina (<5 years)
- Recent myocardial infarction (<5 years)
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase IIa Dose Escalation Pilot Study to Investigate the Safety and Tolerability of Intranasal Insulin in Subjects With Diabetic Polyneuropathy.
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.
Read the detailed description
Diabetic polyneuropathy (DPN) is a common complication of human type I and II diabetes mellitus, identified in up to 50% of diabetic subjects regardless of age or type of diabetes. As the global burden of diabetes heightens due to an epidemic of type II diabetes, the prevalence of DPN will concurrently rise. Clinical features of DPN include loss of sensation, propensity towards traumatic wound formation, neuropathic pain, motor weakness and falls.
At this time there is no specific therapy to arrest or reverse DPN. Previous work has demonstrated not only an absolute reduction in plasma insulin levels in Type I diabetes but also in type II diabetics. At the present, therapy for neuropathic pain associated with DPN is available, but only targets symptom relief and is only partially effective.
Intranasal insulin administration is a novel approach to the treatment of diabetic polyneuropathy (DPN) based on robust basic science research. Intranasal insulin is currently being studied in other conditions and has completed Phase II in subjects with cognitive impairment and mild Alzheimer's disease. Intranasal administration of insulin results in increased penetration into the cerebrospinal fluid and the peripheral nervous system while avoiding systemic absorption. Lack of systemic absorption results in maintenance of normal blood glucose levels in normal healthy subjects.
The objectives of the current study are as follows:
- Primary: To determine the safety and tolerability of intranasal insulin delivery in subjects with type 1 diabetes and DPN.
- Secondary: To determine whether intranasal insulin is efficacious in slowing the progression of DPN.
This study is designed as a double-blind, placebo-controlled, randomized, controlled-dose escalation phase 2 pilot clinical trial.
The duration of the study for each subject is 11 weeks with 6 weeks of blinded study treatment. The study treatment is either active study drug (Novolin Toronto insulin) or placebo (normal saline).
The phases of the study are as follows:
- Screening phase (3 weeks): Potential subjects undergo screening procedures to determine eligibility. Procedures include informed consent, review of medical history, anthropometric measures, vital signs, physical examination (including a neurological assessment), and bloodwork.
- Baseline phase (2 weeks): Eligibility of subjects is confirmed and subjects commence collection of protocol-specified blood glucoses on a daily basis. Nerve conduction tests and corneal confocal microscopy is completed prior to the start of the next phase.
- Treatment phase (6 weeks): Subjects commence the study treatment at the lowest protocol-specified dose. If assigned to Novolin Toronto insulin, this is 20 international units (IU) twice daily (BID). Return visits to the clinic occur every two weeks for dose escalation. The dose increase is 40 IU BID, then 80 IU BID. Subjects assigned to normal saline receive a volume equivalent to the total volume given to the subjects taking insulin. Visits during the treatment phase also include safety bloodwork, serial blood glucose measurements every 15 minutes for a 2 hour period, review of any hypoglycemia, adverse events, changes to concomitant medications, assessment of neuropathy, questionnaires, teaching, and study treatment accountability/compliance assessment. The study completes at the 11 week time period, immediately prior to which the second nerve conduction study and corneal confocal microscopy is completed.
The study protocol is designed to monitor hypoglycemia throughout the baseline and treatment period for all subjects. Any severe hypoglycemia or significant increases in hypoglycemia (>30% compared to the baseline phase) will be reviewed by the Investigator on a case-by-case basis to determine continuation with study treatment. Any subject that undergoes discontinuation of study treatment will be continued to be followed to 11 weeks (without study treatment).
- Conditions
- Diabetic Peripheral Neuropathy
- Being tested
- Novolin Toronto insulin, Normal saline
- Keywords
- Insulin, Diabetic neuropathy, Intranasal administration, Pilot project
- Medical subject headings
- Insulin Resistance, Diabetic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Novolin Toronto insulinDrug
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.
Normal salineDrug
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 .
| Study group | Role | What they receive |
|---|---|---|
| Novolin Toronto insulin | Active comparator | Not described Receives: Drug: Novolin Toronto insulin |
| Normal saline | Placebo comparator | Not described Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hypoglycemia monitoring
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.
Measured: 8 weeks
Secondary outcomes (7)
Treatment satisfaction questionnaire for medication (TSQM)
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.
Measured: 6 weeks
Adverse effects
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.
Measured: 11 weeks
The UTAH early neuropathy scale
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).
Measured: 6 weeks
Corneal confocal microscopy
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).
Measured: 6 weeks
Electrophysiology
The following components will be measured to monitor changes in nerve conduction:
- Sural conduction velocity
- Radial SNAP amplitude
- Radial:Sural SNAP ratio
The nerve conduction tests are completed prior to week 5 (randomization) and immediately prior to week 11 (end of study).
Measured: 6 weeks
McGill pain questionnaire
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).
Measured: 6 weeks
Short Form-36 (SF-36) Quality of life scale
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).
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2011 (estimated)
- Study startAug 2011
- Primary completionJul 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Peripheral NeuropathyStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, DR. LAWRENCE KORNGUT, University of Calgary
- Investigators
- Lawrence M Korngut, MD, FRCPC, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01469559
- Sponsor's protocol ID
- UCALG-IIDPN
- Acronym
- IIDPN
- Status last verified
- Aug 2012
- First submitted
- 8 Nov 2011
- Last updated
- 10 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa Dose Escalation Pilot Study to Investigate the Safety and Tolerability of Intranasal Insulin in Subjects With Diabetic Polyneuropathy.
- ClinicalTrials.gov ID
- NCT01469559
- Acronym / sponsor ID
- IIDPN / UCALG-IIDPN
- Conditions
- Diabetic Peripheral Neuropathy
- Keywords
- Insulin, Diabetic neuropathy, Intranasal administration, Pilot project
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 10 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Diabetic polyneuropathy (DPN) is a common complication of human type I and II diabetes mellitus, identified in up to 50% of diabetic subjects regardless of age or type of diabetes. As the global burden of diabetes heightens due to an epidemic of type II diabetes, the prevalence of DPN will concurrently rise. Clinical features of DPN include loss of sensation, propensity towards traumatic wound formation, neuropathic pain, motor weakness and falls.
At this time there is no specific therapy to arrest or reverse DPN. Previous work has demonstrated not only an absolute reduction in plasma insulin levels in Type I diabetes but also in type II diabetics. At the present, therapy for neuropathic pain associated with DPN is available, but only targets symptom relief and is only partially effective.
Intranasal insulin administration is a novel approach to the treatment of diabetic polyneuropathy (DPN) based on robust basic science research. Intranasal insulin is currently being studied in other conditions and has completed Phase II in subjects with cognitive impairment and mild Alzheimer's disease. Intranasal administration of insulin results in increased penetration into the cerebrospinal fluid and the peripheral nervous system while avoiding systemic absorption. Lack of systemic absorption results in maintenance of normal blood glucose levels in normal healthy subjects.
The objectives of the current study are as follows:
- Primary: To determine the safety and tolerability of intranasal insulin delivery in subjects with type 1 diabetes and DPN.
- Secondary: To determine whether intranasal insulin is efficacious in slowing the progression of DPN.
This study is designed as a double-blind, placebo-controlled, randomized, controlled-dose escalation phase 2 pilot clinical trial.
The duration of the study for each subject is 11 weeks with 6 weeks of blinded study treatment. The study treatment is either active study drug (Novolin Toronto insulin) or placebo (normal saline).
The phases of the study are as follows:
- Screening phase (3 weeks): Potential subjects undergo screening procedures to determine eligibility. Procedures include informed consent, review of medical history, anthropometric measures, vital signs, physical examination (including a neurological assessment), and bloodwork.
- Baseline phase (2 weeks): Eligibility of subjects is confirmed and subjects commence collection of protocol-specified blood glucoses on a daily basis. Nerve conduction tests and corneal confocal microscopy is completed prior to the start of the next phase.
- Treatment phase (6 weeks): Subjects commence the study treatment at the lowest protocol-specified dose. If assigned to Novolin Toronto insulin, this is 20 international units (IU) twice daily (BID). Return visits to the clinic occur every two weeks for dose escalation. The dose increase is 40 IU BID, then 80 IU BID. Subjects assigned to normal saline receive a volume equivalent to the total volume given to the subjects taking insulin. Visits during the treatment phase also include safety bloodwork, serial blood glucose measurements every 15 minutes for a 2 hour period, review of any hypoglycemia, adverse events, changes to concomitant medications, assessment of neuropathy, questionnaires, teaching, and study treatment accountability/compliance assessment. The study completes at the 11 week time period, immediately prior to which the second nerve conduction study and corneal confocal microscopy is completed.
The study protocol is designed to monitor hypoglycemia throughout the baseline and treatment period for all subjects. Any severe hypoglycemia or significant increases in hypoglycemia (>30% compared to the baseline phase) will be reviewed by the Investigator on a case-by-case basis to determine continuation with study treatment. Any subject that undergoes discontinuation of study treatment will be continued to be followed to 11 weeks (without study treatment).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Novolin Toronto insulin | Active comparator | Drug: Novolin Toronto insulin |
| Normal saline | Placebo comparator | Drug: Normal saline |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
- Aged 18 through 70 years (inclusive).
- Body Mass Index (BMI) <30 kilograms/meter2.
Key exclusion criteria (23 listed)
- Any other possible etiology contributing to the neuropathy:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Novolin Toronto insulinSubjects 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. | Drug | Novolin Toronto insulin |
| Normal salineSubjects 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 . | Drug | Normal saline |
Primary outcome
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.
7 secondary outcomes
Treatment satisfaction questionnaire for medication (TSQM)
Time frame: 6 weeks
Adverse effects
Time frame: 11 weeks
The UTAH early neuropathy scale
Time frame: 6 weeks
Corneal confocal microscopy
Time frame: 6 weeks
Electrophysiology
Time frame: 6 weeks
McGill pain questionnaire
Time frame: 6 weeks
Short Form-36 (SF-36) Quality of life scale
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2012.
Related trials for Diabetic Peripheral Neuropathy
Active, not recruiting
Wearable Insoles for Recurrent Diabetic Ulcer Prevention
Diabetes, Peripheral Neuropathy
Recruiting
Effect of 4-7-8 Breathing Technique on Pain and Anxiety During Electromyography in Diabetic Neuropathy
Diabetic Neuropathies, Diabetes Mellitus (Type 2)
Active, not recruiting
Comparative Effects Of Sensory Reweighting And Proprioceptive Facilitation Training On Balance And Fall Risk In Diabetic Peripheral Neuropathy
Diabetic Peripheral Neuropathy (DPN)
Not yet recruiting
Adaptive Gamified Sensory Training on Sensory Function and Limb-Specific Functional Performance in Patients With Diabetic Peripheral Neuropathy
Diabetic Peripheral Neuropathy
Active, not recruiting
Comparative Effects of tDCS and tACS on Pain, Dexterity, and Strength in Diabetic Peripheral Neuropathy
Diabetic Peripheral Neuropathy (DPN)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lawrence M Korngut, MD, FRCPC principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Novolin Toronto insulin and Normal saline in people with Diabetic Peripheral Neuropathy, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hypoglycemia monitoring (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2012.