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Diabetic neuropathy (DN) is the most common chronic complication of diabetes, affecting up to50% of individuals with type 1 diabetes (T1DM).
Multiple pre-clinical and clinical studies demonstrate a pathogenic role for inflammation, especially cytokine production, in the disease course of DN and CAN. This suggests that agents with known anti-inflammatory properties, such as salicylates, may prevent the development of DN and the pain associated with DN. This study builds upon and expands on prior work done by the investigators with salsalate, a pro-drug form of salicylate, as an agent to address inflammatory pathways in people with T1DM.
Diabetic neuropathy (DN) is the most common chronic complication of diabetes, affecting up to50% of individuals with type 1 diabetes (T1DM). DN is a progressive disease, leading to severe morbidity and staggering health care costs. Patients experience poor quality of life due to pain, loss of sensation leading to poor balance, falls and eventual foot deformities with high rates of ulcerations and amputations. While not as commonly diagnosed as DN, cardiovascular autonomic neuropathy (CAN) carries equal morbidity with patients experiencing orthostasis, arrhythmias and premature death).
Despite the high morbidity associated with DN, most randomized clinical trials evaluating therapies for established DN have been disappointing. To date there is no pathogenetic treatment for this condition. The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive control designed to achieve near-normal glycemia is essential in reducing the risk of DN development in type 1 diabetes (8, 9). However, attainable intensive glycemic control, although necessary, is insufficient to prevent adverse nervous system effects, justifying a therapeutic need to identify new drug targets to treat DN early in its course. One such new therapeutic target is inflammation. Multiple pre-clinical and clinical studies demonstrate a pathogenic role for inflammation, especially cytokine production, in the disease course of DN and CAN. This suggests that agents with known anti-inflammatory properties, such as salicylates, may prevent the development of DN and the pain associated with DN. Salsalate, a pro-drug form of salicylate, is a FDA approved drug commonly indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorders. In vitro and in vivo studies and human trials have shown that salicylate therapy is effective in controlling low grade inflammation in diabetes by inhibition of the inhibitor of the κB kinase (IKKβ)/NF-κB pathway. It has a large margin of safety (unlike other salicylates), and a low cost. There is also extensive experience with long-term human use of salsalate.
Several studies show that salsalate causes no greater intestinal occult blood loss than placebo and has no suppressive effects on renal prostaglandin production in contrast to aspirin or NSAIDs. The recently published NIDDK-funded "Targeting Inflammation Using Salsalate in Type 2 Diabetes (TINSAL-T2D)" trial confirmed salutary effects of 3.5 gram/day salsalate on markers of inflammation, glucose control and overall safety after 48 weeks patients with type 2 diabetes. The Investigators' initial NIDDK funded R03 (DK 094499) grant confirmed the safety and feasibility of targeting inflammation with salsalate treatment in T1DM subjects with DN. The Investigators' current study builds upon and expands their initial promising results and will either confirm or refute the therapeutic efficacy of salsalate in a larger T1DM cohort.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Salsalate | Experimental | Salsalate, 1 gram by mouth, 3 times daily (3 grams per day) for 12 months. |
|
| Comparator | Placebo Comparator | Placebo for Salsalate, 2 tablets by mouth, 3 times daily for 12 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Salsalate | Drug | 1 gram, 3 times daily by mouth (total of 3 grams daily) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Skin Biopsy - Intraepidermal Nerve Fiber Density (IENFD) - Distal Thigh | The intraepidermal nerve fiber density (IENFD) is the number of small nerve fibers which can be counted (under a microscope) in a 3 mm piece of skin taken from the distal (lower) thigh. IENFD is a continuous measure of small fiber neuropathy, with high positive and negative predictive values along with a high diagnostic efficiency in differentiating between people with and without neuropathy. People with neuropathy will generally have fewer nerve fibers (lower IENFD) than people without neuropathy. This study examined the change in IENFD after taking salsalate or a placebo daily for 12 months in people with diabetic neuropathy. Skin samples taken at the start of the study were compared to skin samples taken 12 months later to see if salsalate caused an increase in IENFD (suggesting improvement), or smaller decrease in IENFD (suggesting slower progression of neuropathy) relative to placebo. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Measures of Cardiac Autonomic Neuropathy (CAN) - Valsalva Ratio | Valsalva Ratio is the ratio of max tachycardia to max bradycardia caused by Valsalva maneuver | Baseline and 12 Months |
| Measures of Cardiac Autonomic Neuropathy (CAN) - Expiration/Inspiration Ratio |
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Inclusion Criteria
Exclusion Criteria
In addition, subjects with concurrent chicken pox, influenza, flu-like symptoms or other symptomatic viral illnesses should not be enrolled in the study until the illness or condition has resolved.
Subjects with known or suspected hypersensitivity to lidocaine or epinephrine may not be able to participate as these agents are used for local anesthesia during skin biopsies. The study investigators should consider the nature and severity of past reported reactions to these agents, and may consider alternative anesthesia options for local anesthesia on a case by case basis.
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| Name | Affiliation | Role |
|---|---|---|
| Rodica Pop-Busui, MD, PhD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Veterans Administration Ann Arbor Health Center | Ann Arbor | Michigan | 48105 | United States | ||
| University of Michigan Health System |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39727210 | Derived | Ang L, Gunaratnam S, Huang Y, Dillon BR, Martin CL, Burant A, Reiss J, Blakely P, Vasbinder A, Zhao L, Mizokami-Stout K, Tang Y, Feldman EL, Doria A, Spino C, Banerjee M, Hayek SS, Pop-Busui R. Inflammatory Markers and Measures of Cardiovascular Autonomic Neuropathy in Type 1 Diabetes. J Am Heart Assoc. 2025 Jan 7;14(1):e036787. doi: 10.1161/JAHA.124.036787. Epub 2024 Dec 27. |
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Ninety-six (96) people underwent eligibility screening to participate in the study. Of these, 64 satisfied the eligibility criteria for participation, and 61 were randomly assigned and entered the treatment phase of the study (and shown as started in the table below). Three of the 64 eligible participants did not complete visit 2, and therefore, were not assigned to treatment. Informed consent was obtained from all participants at the time of their screening visit.
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| ID | Title | Description |
|---|---|---|
| FG000 | Salsalate | Salsalate, 1 gram by mouth, 3 times daily (3 grams per day) for 12 months. Salsalate: 1 gram, 3 times daily by mouth (total of 3 grams daily) |
| FG001 | Comparator | Placebo for Salsalate, 2 tablets by mouth, 3 times daily for 12 months PLACEBO: Placebo for Salsalate; 2 Tablets, 3 times daily by mouth (total of 3 grams daily) |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Salsalate | Salsalate, 1 gram by mouth, 3 times daily (3 grams per day) for 12 months. Salsalate: 1 gram, 3 times daily by mouth (total of 3 grams daily) |
| BG001 | Comparator | Placebo for Salsalate, 2 tablets by mouth, 3 times daily for 12 months PLACEBO: Placebo for Salsalate; 2 Tablets, 3 times daily by mouth (total of 3 grams daily) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Skin Biopsy - Intraepidermal Nerve Fiber Density (IENFD) - Distal Thigh | The intraepidermal nerve fiber density (IENFD) is the number of small nerve fibers which can be counted (under a microscope) in a 3 mm piece of skin taken from the distal (lower) thigh. IENFD is a continuous measure of small fiber neuropathy, with high positive and negative predictive values along with a high diagnostic efficiency in differentiating between people with and without neuropathy. People with neuropathy will generally have fewer nerve fibers (lower IENFD) than people without neuropathy. This study examined the change in IENFD after taking salsalate or a placebo daily for 12 months in people with diabetic neuropathy. Skin samples taken at the start of the study were compared to skin samples taken 12 months later to see if salsalate caused an increase in IENFD (suggesting improvement), or smaller decrease in IENFD (suggesting slower progression of neuropathy) relative to placebo. | The analysis is limited to participants with analyzable skin samples at both baseline and at 12 months. Participants who withdrew or were lost to follow-up prior to 12 months are not included in this analysis. | Posted | Mean | Standard Deviation | Percentage change in IENFD | 12 months |
Adverse events were assessed at each participant visit starting from screening (Visit 1) to the final study visit (Visit 7), typically about 12 months.
Adverse event reporting is described in the protocol.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Salsalate | Salsalate, 1 gram by mouth, 3 times daily (3 grams per day) for 12 months. Salsalate: 1 gram, 3 times daily by mouth (total of 3 grams daily) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CARDIOVASCULAR EVENTS | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Endocrine, Endocrine/Infectious, Endocrine/Gastrointestinal | Endocrine disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rodica Pop-Busui, MD, PhD | The University of Michigan | Phone 734-647-9809 | rpbusui@med.umich.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 10, 2022 | Jun 24, 2024 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 16, 2023 | Jul 6, 2023 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D010523 | Peripheral Nervous System Diseases |
| D010146 | Pain |
| D007249 | Inflammation |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C014182 | salicylsalicylic acid |
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| PLACEBO | Drug | Placebo for Salsalate; 2 Tablets, 3 times daily by mouth (total of 3 grams daily) |
|
The expiration/inspiration ratio (E/I) ratio is measured during a period of slow, deep breathing (6 breaths per minute). It is the average heart rate increase divided by the average heart rate decrease over 6 breath cycles per minute |
| Baseline and 12 Months |
| Measures of Cardiac Autonomic Neuropathy (CAN) - 30:15 Ratio | Ratio of max RR interval ~30 heartbeats to min RR interval ~15 heartbeats | Baseline and 12 Months |
| Measures of Cardiac Autonomic Neuropathy (CAN) - SDNN | Standard deviation of NN intervals. The value indicates the amount of variability in the interval between each heart beat (the R-R interval). Value is expressed in milliseconds | Baseline and 12 Months |
| Measures of Cardiac Autonomic Neuropathy (CAN) - RMSSD | Root mean square of successive differences between normal heartbeats. It represents the average variation between the beat to beat intervals. The result is expressed in milliseconds. | Baseline and 12 Months |
| Nerve Conduction | Nerve Conduction Studies of the sural, peroneal, and ulnar nerves will be obtained at screening and 12 months. Nerve conduction studies are used to detect abnormalities in how the nerves are working. Nerve Conduction is represented as number of nerves with abnormal nerve conduction per participant. | Baseline and 12 months |
| Quantitative Sensory Testing - Just Noticeable Difference in COLD Detection | The Just Noticeable Difference (JND) in response to a cold stimulus applied to the top of the foot was measured using the CASE IV System. The range of JND values is from 1 to 25. A JND value of 1 means a person can detect temperature decrease of 0.063 degrees Celsius while a JND value of 25 means that the temperature has to drop by 20 degrees Celsius colder than before the person can notice the change in temperature. People with neuropathy will have higher JND values than people without neuropathy, indicating that they are less able to detect changes in temperature. For this study, the cold JND at the first visit was compared to the JND at the second visit to see if JND for cold detection after 12 months of treatment with salsalate or placebo. | Baseline and 12 months |
| Quantitative Sensory Testing - Just Noticeable Difference- Vibration | The Just Noticeable Difference (JND) in response to a vibrating stimulus (probe) applied to the toe was measured using the CASE IV System. The range of JND values is from 1 to 25. A JND value of 1 means a person can detect very light vibration (vibration magnitude of 0.106 micrometers) while a 25 means a much stronger vibration stimulus had to be applied to be detected (vibration magnitude of 576.603 micrometers). People with neuropathy will have higher JND values than people without neuropathy, indicating that they are less able to detect vibration. For this study, the vibration JND at the first visit was compared to the vibration JND at the second visit to see if the values had changed after 12 months. | Baseline and 12 months |
| Diabetic Neuropathy Symptoms | DN symptoms as evaluated by the Neuropathy Total Symptom Score-6 (NTSS-6). The NTSS-6 has 6 questions with individual scores between 0 and 3.66. Cumulative scores range from 0 to 21.96 with 21.96 being the worst neuropathy and 0 being no neuropathy. | Baseline to 12 months |
| Survey of Autonomic Symptoms (SAS) | Survey of Autonomic Symptoms (SAS) is a 12-item questionnaire. The range of scores is 0-60 for men and 0-55 for women, with higher scores indicating a higher degree of autonomic symptoms. Men and Women were not analyzed separately due to the comparable gender distribution between arms. | Baseline to 12 months |
| The DCCT/EDIC Structured Neurological Examination | The DCCT/EDIC Structured Neurological Examination is an examination that determines whether or not someone has evidence of neuropathy from diabetes. The examination categorizes patients into 3 categories: Definite Clinically Evident Peripheral Neuropathy, Possible Clinically Evident Peripheral Neuropathy, and No Clinically Evident Peripheral Neuropathy. | Baseline and 12 months |
| NeuroQOL | NeuroQOL is a self-administered questionnaire that measures the impact of neuropathy symptoms, especially those affecting the feet and legs, on quality of life. Shown are results from baseline, 6 and 12 months for the item "Overall, I would say problem with my feet reduced my quality of life". Responses are on a five-point scale (1 = "not at all" up to 5 = "very much") with higher values indicating a greater reduction in quality of life. | Baseline, 6 months and 12 months |
| Neuropathic Pain Scale | The Neuropathic Pain Scale is a questionnaire where participants rate the intensity of their pain and the quality of the pain (e.g., burning, aching, stabbing). Higher scores indicate greater pain. Scores range from 0 to 100. | baseline, 6 months, 12 months |
| The Berg Balance Scale | The Berg Balance Scale measures balance in 14 separate activities of daily living such as going from sitting-to-stand and standing on one leg; the unipedal stance portion that had been shown to be particularly reflective of neuropathy-related mobility loss. Scores range from 0 to 56, where lower scores indicate worst mobility and balance and 56 indicates best mobility and balance. | Baseline and 12 months |
| 8 Foot Up and Go Test | The 8 Foot Up and Go Test, a test of functional mobility that assesses the time needed for a subject to arise from sitting position, walk 8 ft and turn 180 degrees around a cone and return sitting; Test results are expressed in seconds. The test is performed twice and the fastest speed is reported. | Baseline and 12 months |
| The Modified Falls Efficacy Scale | The Modified Falls Efficacy Scale assessing patient's self-reported ability to perform activities of daily living (e.g. get dressed/ undressed, walking, shopping). Scores range from 0 to 10 on 14 items. Resulting score is average score across those 14 questions, resulting in a score from 0 to 10. 0 represents the participant being not at all confident that they can complete activities without falling and 10 represents participant being entirely confident that they can complete activities without falling. | Baseline and 12 months |
| Ann Arbor |
| Michigan |
| 48109 |
| United States |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Salsalate | Salsalate, 1 gram by mouth, 3 times daily (3 grams per day) for 12 months. Salsalate: 1 gram, 3 times daily by mouth (total of 3 grams daily) |
| OG001 | Comparator | Placebo for Salsalate, 2 tablets by mouth, 3 times daily for 12 months PLACEBO: Placebo for Salsalate; 2 Tablets, 3 times daily by mouth (total of 3 grams daily) |
|
|
| Secondary | Measures of Cardiac Autonomic Neuropathy (CAN) - Valsalva Ratio | Valsalva Ratio is the ratio of max tachycardia to max bradycardia caused by Valsalva maneuver | This analysis is limited to participants who completed the valsalva maneuver successfully at both the baseline and final study visits. Participants who withdrew (N=2) or were lost to follow-up (4) are not included in the analysis. | Posted | Mean | Standard Deviation | ratio | Baseline and 12 Months |
|
|
|
| Secondary | Measures of Cardiac Autonomic Neuropathy (CAN) - Expiration/Inspiration Ratio | The expiration/inspiration ratio (E/I) ratio is measured during a period of slow, deep breathing (6 breaths per minute). It is the average heart rate increase divided by the average heart rate decrease over 6 breath cycles per minute | Only participants with both baseline and 12 month data were included in analysis. Participants who withdrew (N=2) or were lost to follow-up (N=4) are not included in the analysis. | Posted | Mean | Standard Deviation | ratio | Baseline and 12 Months |
|
|
|
|
| Secondary | Measures of Cardiac Autonomic Neuropathy (CAN) - 30:15 Ratio | Ratio of max RR interval ~30 heartbeats to min RR interval ~15 heartbeats | Only participants with both baseline and 12 month data were included in analysis. Participants who withdrew (N=2) or were lost to follow-up (N=4) are not included in the analysis. | Posted | Mean | Standard Deviation | ratio | Baseline and 12 Months |
|
|
|
| Secondary | Measures of Cardiac Autonomic Neuropathy (CAN) - SDNN | Standard deviation of NN intervals. The value indicates the amount of variability in the interval between each heart beat (the R-R interval). Value is expressed in milliseconds | Only participants with both baseline and 12 month data were included in analysis. Participants who withdrew (N=2) or were lost to follow-up (N=4) are not included in the analysis. | Posted | Mean | Standard Deviation | milliseconds | Baseline and 12 Months |
|
|
|
| Secondary | Measures of Cardiac Autonomic Neuropathy (CAN) - RMSSD | Root mean square of successive differences between normal heartbeats. It represents the average variation between the beat to beat intervals. The result is expressed in milliseconds. | Only participants with both baseline and 12 month data were included in analysis. Participants who withdrew (N=2) or were lost to follow-up (N=4) are not included in the analysis. | Posted | Mean | Standard Deviation | milliseconds | Baseline and 12 Months |
|
|
|
| Secondary | Nerve Conduction | Nerve Conduction Studies of the sural, peroneal, and ulnar nerves will be obtained at screening and 12 months. Nerve conduction studies are used to detect abnormalities in how the nerves are working. Nerve Conduction is represented as number of nerves with abnormal nerve conduction per participant. | All participants are included in the baseline analysis. Data are not available for participants who withdrew (N=2) or were lost to follow-up (4) prior to month 12, and for one additional participant who was unwilling to undergo the nerve conduction test at the final study visit. | Posted | Count of Participants | Participants | Baseline and 12 months |
|
|
|
| Secondary | Quantitative Sensory Testing - Just Noticeable Difference in COLD Detection | The Just Noticeable Difference (JND) in response to a cold stimulus applied to the top of the foot was measured using the CASE IV System. The range of JND values is from 1 to 25. A JND value of 1 means a person can detect temperature decrease of 0.063 degrees Celsius while a JND value of 25 means that the temperature has to drop by 20 degrees Celsius colder than before the person can notice the change in temperature. People with neuropathy will have higher JND values than people without neuropathy, indicating that they are less able to detect changes in temperature. For this study, the cold JND at the first visit was compared to the JND at the second visit to see if JND for cold detection after 12 months of treatment with salsalate or placebo. | Two enrolled participants are missing baseline data for this specific outcome measure as the device (CASE IV) could not record a response (technical limitations). The 12 month data excludes participants who withdrew (N=2) or were lost to follow up (N=4), one participant who declined the test at study end, and excludes results for 5 participants due to technical limitations of the device. | Posted | Mean | Standard Deviation | JND Units | Baseline and 12 months |
|
|
|
| Secondary | Quantitative Sensory Testing - Just Noticeable Difference- Vibration | The Just Noticeable Difference (JND) in response to a vibrating stimulus (probe) applied to the toe was measured using the CASE IV System. The range of JND values is from 1 to 25. A JND value of 1 means a person can detect very light vibration (vibration magnitude of 0.106 micrometers) while a 25 means a much stronger vibration stimulus had to be applied to be detected (vibration magnitude of 576.603 micrometers). People with neuropathy will have higher JND values than people without neuropathy, indicating that they are less able to detect vibration. For this study, the vibration JND at the first visit was compared to the vibration JND at the second visit to see if the values had changed after 12 months. | Three enrolled participants (of 61 total enrolled) are missing baseline data for this specific measure as the CASEIV device could not record a response (technical limitations). The 12 month data excludes participants who withdrew (N=2) or were lost to follow up (N=4), one participant who declined the test at study end, and for 4 participants due to technical limitations of the CASE IV device. | Posted | Mean | Standard Deviation | JND Units | Baseline and 12 months |
|
|
|
| Secondary | Diabetic Neuropathy Symptoms | DN symptoms as evaluated by the Neuropathy Total Symptom Score-6 (NTSS-6). The NTSS-6 has 6 questions with individual scores between 0 and 3.66. Cumulative scores range from 0 to 21.96 with 21.96 being the worst neuropathy and 0 being no neuropathy. | Baseline data is available for all enrolled participants. 12 months data excludes participants who withdrew (N=2),or were lost to follow-up (N=4) and 2 participants with incomplete or missing surveys at 12 months. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 12 months |
|
|
|
| Secondary | Survey of Autonomic Symptoms (SAS) | Survey of Autonomic Symptoms (SAS) is a 12-item questionnaire. The range of scores is 0-60 for men and 0-55 for women, with higher scores indicating a higher degree of autonomic symptoms. Men and Women were not analyzed separately due to the comparable gender distribution between arms. | Baseline data is available for all enrolled participants. 12 months data excludes participants who withdrew (N=2), or were lost to follow-up (N=4) and 2 participants with incomplete or missing surveys at 12 months. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 12 months |
|
|
|
| Secondary | The DCCT/EDIC Structured Neurological Examination | The DCCT/EDIC Structured Neurological Examination is an examination that determines whether or not someone has evidence of neuropathy from diabetes. The examination categorizes patients into 3 categories: Definite Clinically Evident Peripheral Neuropathy, Possible Clinically Evident Peripheral Neuropathy, and No Clinically Evident Peripheral Neuropathy. | Baseline data is available for all enrolled participants. 12 months data excludes participants who withdrew (N=2), or were lost to follow-up (N=4) and 2 participants who did not complete the examination at the 12 month time point. | Posted | Count of Participants | Participants | Baseline and 12 months |
|
|
|
| Secondary | NeuroQOL | NeuroQOL is a self-administered questionnaire that measures the impact of neuropathy symptoms, especially those affecting the feet and legs, on quality of life. Shown are results from baseline, 6 and 12 months for the item "Overall, I would say problem with my feet reduced my quality of life". Responses are on a five-point scale (1 = "not at all" up to 5 = "very much") with higher values indicating a greater reduction in quality of life. | The survey was completed by all enrolled participants at baseline. Six (6) and 12 month values are shown for all participants who had not withdrawn from the study or were lost to follow-up prior to the survey administration. One participant who completed the study, did not complete the survey at month 12. | Posted | Mean | Standard Deviation | score on a scale | Baseline, 6 months and 12 months |
|
|
|
| Secondary | Neuropathic Pain Scale | The Neuropathic Pain Scale is a questionnaire where participants rate the intensity of their pain and the quality of the pain (e.g., burning, aching, stabbing). Higher scores indicate greater pain. Scores range from 0 to 100. | Baseline data is available for all enrolled participants. Six (6) and12 month data excludes those participants who had withdrawn, or had been declared lost to follow-up prior to the visit at which the survey was administered. | Posted | Mean | Standard Deviation | score on a scale | baseline, 6 months, 12 months |
|
|
|
| Secondary | The Berg Balance Scale | The Berg Balance Scale measures balance in 14 separate activities of daily living such as going from sitting-to-stand and standing on one leg; the unipedal stance portion that had been shown to be particularly reflective of neuropathy-related mobility loss. Scores range from 0 to 56, where lower scores indicate worst mobility and balance and 56 indicates best mobility and balance. | Data from all enrolled participants is shown at baseline. The 12 month data excludes patients who had withdrawn (N=2) or were lost to follow-up (N=4), and an additional two participants who did not complete measure at the final visit. | Posted | Mean | Standard Deviation | score on a scale | Baseline and 12 months |
|
|
|
| Secondary | 8 Foot Up and Go Test | The 8 Foot Up and Go Test, a test of functional mobility that assesses the time needed for a subject to arise from sitting position, walk 8 ft and turn 180 degrees around a cone and return sitting; Test results are expressed in seconds. The test is performed twice and the fastest speed is reported. | Baseline analysis includes all enrolled participants. The final visit analysis excludes participants who withdrew (N = 2) or were lost to follow-up (N=4), and 2 participants who did not complete the measure at their final study visit. | Posted | Mean | Standard Deviation | seconds | Baseline and 12 months |
|
|
|
| Secondary | The Modified Falls Efficacy Scale | The Modified Falls Efficacy Scale assessing patient's self-reported ability to perform activities of daily living (e.g. get dressed/ undressed, walking, shopping). Scores range from 0 to 10 on 14 items. Resulting score is average score across those 14 questions, resulting in a score from 0 to 10. 0 represents the participant being not at all confident that they can complete activities without falling and 10 represents participant being entirely confident that they can complete activities without falling. | Data from all enrolled participants is shown at baseline. The 12 month data excludes patients who had withdrawn (N=2) or were lost to follow-up (N=4), and an additional two participants who did not complete measure at the final visit. | Posted | Mean | Standard Deviation | score on a scale | Baseline and 12 months |
|
|
|
| 0 |
| 37 |
| 6 |
| 37 |
| 30 |
| 37 |
| EG001 | Comparator | Placebo for Salsalate, 2 tablets by mouth, 3 times daily for 12 months PLACEBO: Placebo for Salsalate; 2 Tablets, 3 times daily by mouth (total of 3 grams daily) | 0 | 24 | 4 | 24 | 19 | 24 |
| HYPERGLYCEMIA/DIABETIC KETOACIDOSIS | Endocrine disorders | Systematic Assessment |
|
| NAUSEA AND VOMITING | Gastrointestinal disorders | Systematic Assessment | SEVERE NAUSEA AND VOMITING IN PATIENT WITH KNOWN GASTROPARESIS |
|
| ALLERGIC REACTION | Immune system disorders | Systematic Assessment | SEVERE ALLERGIC REACTION TO LAUNDRY SOAP |
|
| INFECTION | Infections and infestations | Systematic Assessment |
|
| INJURY | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Cardiac, Cardiovascular, Circulatory disorders | Cardiac disorders | Systematic Assessment |
|
| Gastrointestinal adverse event | Gastrointestinal disorders | Systematic Assessment |
|
| Infection | Infections and infestations | Systematic Assessment |
|
| Musculoskeletal adverse event | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Otorhinolaryngologic adverse event | Ear and labyrinth disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010335 | Pathologic Processes |
| Participants with 1 Abnormal Nerve |
|
| Participants with 2 Abnormal Nerves |
|
| Participants with 3 Abnormal Nerves |
|
| 12 months |
|
|
| 12 Month |
|
|
| 12 Month |
|
|
| 12 Month |
|
|
| 12 Months |
|
|
| Possible Clinically Evident Peripheral Neuropathy |
|
| No Clinically Evident Peripheral Neuropathy |
|
| 12 Months |
|
|
| 6 Months |
|
|
| 12 Months |
|
|
| 6 Month |
|
|
| 12 Month |
|
|
| 12 Months |
|
|
| 12 Month |
|
|
| 12 Months |
|
|