Peripheral NeuropathyPhase 2SALPNCT01480297
Pilot Study to Determine Effects of Salsalate in Type 1 Diabetes and Painful Peripheral Neuropathy
A Phase 2 study testing Salsalate in people with Peripheral Neuropathy and Type 1 Diabetes, run by University of Michigan at 1 site in United States.
Trial summary
This 12 week study will examine the effects of daily Salsalate treatment on markers of neuropathic pain and intra-epidermal nerve fiber density. the study is being done in people with type 1 diabetes with signs and symptoms of peripheral neuropathy. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Peripheral Neuropathy, Type 1 Diabetes
- What is being tested?
- Salsalate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2011to Sep 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Type 1 diabetes (T1D)
- Peripheral neuropathy with symptoms of pain, or with other uncomfortable symptoms (e.g., burning, prickling).
- 18 to 70 years old
- Stable insulin treatment program for at least the past 3 months.
- Abnormal nerve conduction studies (based on study screening examination)
- Willing and able to take an oral (by mouth) medication 3 times per day for 3 months.
- WOMEN using an appropriate method of contraception during the course of the study (hormonal, IUD, or diaphragm.
- Willing and able to provide written informed consent for study participation.
Who cannot join
- Neuropathy from a cause other than diabetes.
- Allergy to salsalate or similar medications (aspirin, non-steroidal anti-inflammatory medicines like ibuprofen and naproxen).
- Currently on blood thinning agents such as Coumadin, Heparin, Plavix, Pradaxa, high-dose aspirin (more than 325 mg daily).
- Any severe low blood sugar episodes in the past 6 months (needed assistance to treat).
- Diabetic ketoacidosis in the past 6 months.
- Severe neuropathy, or have had an ulcer or amputation on either foot or either leg.
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- Creatinine level (a measure of kidney function is greater than 1.4 mg/dl (for women) or greater than 1.5 mg/dl (for men) or your estimated GFR is under 60.
- Albumin in your urine or other signs of reduced kidney function.
- Liver enzymes (including ALT, AST and Bilirubin) levels are more than 2 and ½ times the upper limit of normal.
- Blood platelets are less than 100,000 at the time of screening.
- Organ transplant (lung, kidney, heart, pancreas, liver).
- Chronic immunosuppressive therapy, for example, daily prednisone or other steroids, methotrexate, Imuran, CellCept. This includes daily, or recurrent use of oral steroids used to treat asthma.
- Regular NSAID medications (e.g., Naproxen, Ibuprofen) use. If used occasionally, you will be asked to not use them during the study.
- History of drug or alcohol abuse, or if you take more than 10 alcoholic drinks per week.
- History of stomach ulcers or bleeding from your bowel.
- Heart attack, heart bypass surgery, heart failure or a stroke EVER.
- Current treatment for any cancer (other than basal cell or squamous cell skin cancer).
- Treatment with lithium.
- Ever had Reyes' syndrome.
- Pregnant, nursing, or planning to become pregnant during the time of the study.
- Allergic to lidocaine or epinephrine (used for numbing skin prior to biopsies).
- Keloid scarring in the past.
- Receiving other experimental treatments.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study to Determine the Effects of 12 Weeks of Treatment With Salsalate on Measures of Peripheral Neuropathy in Type 1 Diabetes
This 12 week study will examine the effects of daily Salsalate treatment on markers of neuropathic pain and intra-epidermal nerve fiber density. the study is being done in people with type 1 diabetes with signs and symptoms of peripheral neuropathy.
Read the detailed description
This project will be used to establish preliminary data for a planned NIH-sponsored multicenter study of the effects of salsalate on diabetic neuropathy (DN) in people with type 1 diabetes. Diabetic peripheral neuropathy (DN) ultimately affects one-half of the patients with type 1 diabetes (T1DM) and is a major cause of disability, high mortality, and poor quality of life. Although intensive glucose control has proven efficacy in delaying or preventing DN in T1DM and type 2 diabetes (T2DM), most people with diabetes do not reach and maintain glycemic levels needed to achieve these benefits. In addition, many patients with diabetes still develop diabetic complications, including DN, despite good glucose control. For DN, no disease modifying treatment other than glycemic control is available. Therefore, it is essential to identify new drug targets and to treat DN as early as possible in its course.
The investigators planned, multi-center study will be the first to determine the effect of an anti-inflammatory agent, salsalate, on DN development and progression, and on DN pain in type 1 diabetes. This proof-of-concept pilot study will measure the effects of short term (12 week) treatment with Salsalate on novel and on established measures of peripheral neuropathy. Ultimately, this may permit measurement of treatment effects over a shorter period of time than by using established measures such as nerve conduction studies. Salsalate, a prodrug form of salicylate, is used to treat osteoarthritis and other rheumatologic conditions. It is highly effective in modulating the IKKβ/NF-κB pathway, with a large margin of safety, and has a glucose lowering effect in patients with type 2 diabetes. The IKKβ/NF-κB pathway is unique in that it is implicated in both the pathogenesis of nerve fiber loss as well as pain in DN. The proposed study design employs a quantifiable early measure of DN, IENFD of the thigh, allowing for accurate assessment of actual nerve fiber density over time.
In the pilot study, biomarkers of pain found in IENF's as well as IENFD will be measured pre and post 3 months of treatment with Salsalate, 3 grams daily.
- Conditions
- Peripheral Neuropathy, Type 1 Diabetes
- Being tested
- Salsalate
- Keywords
- Pain, Neuropathy, Diabetes type 1
- Medical subject headings
- Peripheral Nervous System Diseases, Diabetes Mellitus, Type 1, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SalsalateDrug
Also called Salsalate (Amneal Pharmaceuticals)
Salsalate 3 grams daily (1 gram TID with meals)
| Study group | Role | What they receive |
|---|---|---|
| Salsalate | Experimental | All subjects will take Salsalate, 3 grams daily (as 3 divided doses of 1 gram with breakfast, lunch and dinner). Receives: Drug: Salsalate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intra-epidermal Nerve Fiber Density (IENFD) Fibers Per mm
Intra-epidermal Nerve Fiber Density (IENFD) was measured at two anatomic locations (thigh and ankle) at baseline and after 12 weeks of treatment with Salsalate. IENFD is expressed as fibers per mm. Means and standard deviations are shown.
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2011 (estimated)
- Study startNov 2011
- Primary completionApr 2012
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Peripheral NeuropathyStudies of the same condition, open and under way.
- More trials run by University of MichiganThe 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rodica Pop-Busui, University of Michigan
- Investigators
- Rodica Pop-Busui, MD, PhD, Principal investigator, University of Michigan, Department of Internal Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01480297
- Sponsor's protocol ID
- SALP
- Acronym
- SALP
- Status last verified
- Apr 2015
- First submitted
- 23 Nov 2011
- Last updated
- 24 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Determine the Effects of 12 Weeks of Treatment With Salsalate on Measures of Peripheral Neuropathy in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT01480297
- Acronym / sponsor ID
- SALP / SALP
- Conditions
- Peripheral Neuropathy, Type 1 Diabetes
- Keywords
- Pain, Neuropathy, Diabetes type 1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- Apr 2012 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 28 Nov 2011 (estimated)
- Results
- Posted 24 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This 12 week study will examine the effects of daily Salsalate treatment on markers of neuropathic pain and intra-epidermal nerve fiber density. the study is being done in people with type 1 diabetes with signs and symptoms of peripheral neuropathy.
Detailed description
This project will be used to establish preliminary data for a planned NIH-sponsored multicenter study of the effects of salsalate on diabetic neuropathy (DN) in people with type 1 diabetes. Diabetic peripheral neuropathy (DN) ultimately affects one-half of the patients with type 1 diabetes (T1DM) and is a major cause of disability, high mortality, and poor quality of life. Although intensive glucose control has proven efficacy in delaying or preventing DN in T1DM and type 2 diabetes (T2DM), most people with diabetes do not reach and maintain glycemic levels needed to achieve these benefits. In addition, many patients with diabetes still develop diabetic complications, including DN, despite good glucose control. For DN, no disease modifying treatment other than glycemic control is available. Therefore, it is essential to identify new drug targets and to treat DN as early as possible in its course.
The investigators planned, multi-center study will be the first to determine the effect of an anti-inflammatory agent, salsalate, on DN development and progression, and on DN pain in type 1 diabetes. This proof-of-concept pilot study will measure the effects of short term (12 week) treatment with Salsalate on novel and on established measures of peripheral neuropathy. Ultimately, this may permit measurement of treatment effects over a shorter period of time than by using established measures such as nerve conduction studies. Salsalate, a prodrug form of salicylate, is used to treat osteoarthritis and other rheumatologic conditions. It is highly effective in modulating the IKKβ/NF-κB pathway, with a large margin of safety, and has a glucose lowering effect in patients with type 2 diabetes. The IKKβ/NF-κB pathway is unique in that it is implicated in both the pathogenesis of nerve fiber loss as well as pain in DN. The proposed study design employs a quantifiable early measure of DN, IENFD of the thigh, allowing for accurate assessment of actual nerve fiber density over time.
In the pilot study, biomarkers of pain found in IENF's as well as IENFD will be measured pre and post 3 months of treatment with Salsalate, 3 grams daily.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Salsalate | Experimental | Drug: SalsalateAll subjects will take Salsalate, 3 grams daily (as 3 divided doses of 1 gram with breakfast, lunch and dinner). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Type 1 diabetes (T1D)
- Peripheral neuropathy with symptoms of pain, or with other uncomfortable symptoms (e.g., burning, prickling).
- 18 to 70 years old
- Stable insulin treatment program for at least the past 3 months.
- Abnormal nerve conduction studies (based on study screening examination)
Key exclusion criteria (23 listed)
- Neuropathy from a cause other than diabetes.
- Allergy to salsalate or similar medications (aspirin, non-steroidal anti-inflammatory medicines like ibuprofen and naproxen).
- Currently on blood thinning agents such as Coumadin, Heparin, Plavix, Pradaxa, high-dose aspirin (more than 325 mg daily).
- Any severe low blood sugar episodes in the past 6 months (needed assistance to treat).
- Diabetic ketoacidosis in the past 6 months.
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 |
|---|---|---|
| SalsalateAlso: Salsalate (Amneal Pharmaceuticals)Salsalate 3 grams daily (1 gram TID with meals) | Drug | Salsalate |
Primary outcome
Intra-epidermal Nerve Fiber Density (IENFD) Fibers Per mm
Time frame: Baseline and 12 weeks
Intra-epidermal Nerve Fiber Density (IENFD) was measured at two anatomic locations (thigh and ankle) at baseline and after 12 weeks of treatment with Salsalate. IENFD is expressed as fibers per mm. Means and standard deviations are shown.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Rodica Pop-Busui, MD, PhD principal investigator
University of Michigan, Department of Internal Medicine
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 Salsalate in people with Peripheral Neuropathy and Type 1 Diabetes, run by University of Michigan at 1 site in United States.
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 8 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 24 Apr 2015. 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 United States. 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. 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?
Yes. Results are posted in the registry (first posted 24 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Intra-epidermal Nerve Fiber Density (IENFD) Fibers Per mm (time frame: Baseline and 12 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 24 Apr 2015.