SALP: Pilot Study to Determine Effects of Salsalate in Type 1 Diabetes and Painful Peripheral Neuropathy
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Salsalate All subjects will take Salsalate, 3 grams daily (as 3 divided doses of 1 gram with breakfast, lunch and dinner). |
Drug: Salsalate
Salsalate 3 grams daily (1 gram TID with meals)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Intra-epidermal Nerve Fiber Density (IENFD) Fibers Per mm [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
Exclusion Criteria:
-
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.
-
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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
Sponsors and Collaborators
- University of Michigan
Investigators
- Principal Investigator: Rodica Pop-Busui, MD, PhD, University of Michigan, Department of Internal Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SALP
Study Results
Participant Flow
| Recruitment Details | Recruitment was completed in 3 months time. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Salsalate |
|---|---|
| Arm/Group Description | All subjects will take Salsalate, 3 grams daily (as 3 divided doses of 1 gram with breakfast, lunch and dinner). Salsalate: Salsalate 3 grams daily (1 gram TID with meals) |
| Period Title: Overall Study | |
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Salsalate |
|---|---|
| Arm/Group Description | All subjects will take Salsalate, 3 grams daily (as 3 divided doses of 1 gram with breakfast, lunch and dinner). Salsalate: Salsalate 3 grams daily (1 gram TID with meals) |
| Overall Participants | 8 |
| Age (Years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Years] |
57.0
(5.7)
|
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
7
87.5%
|
| >=65 years |
1
12.5%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
3
37.5%
|
| Male |
5
62.5%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
8
100%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
8
100%
|
Outcome Measures
| Title | Intra-epidermal Nerve Fiber Density (IENFD) Fibers Per mm |
|---|---|
| Description | 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. |
| Time Frame | Baseline and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Type 1 diabetes with painful neuropathy |
| Arm/Group Title | Salsalate |
|---|---|
| Arm/Group Description | All subjects will take Salsalate, 3 grams daily (as 3 divided doses of 1 gram with breakfast, lunch and dinner). Salsalate: Salsalate 3 grams daily (1 gram TID with meals) |
| Measure Participants | 8 |
| Baseline Thigh IENFD(fibers per mm) |
6.3
(5.4)
|
| Baseline Ankle IENFD(fibers per mm) |
3.0
(3.3)
|
| 12 Week Thigh IENFD(fibers per mm) |
5.2
(4.4)
|
| 12 Week Ankle IENFD(fibers per mm) |
3.0
(3.5)
|
Adverse Events
| Time Frame | 3 months | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Salsalate | |
| Arm/Group Description | All subjects will take Salsalate, 3 grams daily (as 3 divided doses of 1 gram with breakfast, lunch and dinner). Salsalate: Salsalate 3 grams daily (1 gram TID with meals) | |
All Cause Mortality |
||
| Salsalate | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Salsalate | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/8 (12.5%) | |
| Metabolism and nutrition disorders | ||
| Severe Hypoglycemia | 1/8 (12.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Salsalate | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/8 (75%) | |
| Ear and labyrinth disorders | ||
| Tinnitus | 3/8 (37.5%) | 3 |
| Endocrine disorders | ||
| Hot Flashes | 1/8 (12.5%) | 1 |
| Eye disorders | ||
| Cataract Removal | 1/8 (12.5%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Upper Respiratory Symptoms | 2/8 (25%) | 2 |
| Skin and subcutaneous tissue disorders | ||
| Skin Biopsy of Suspicious Lesion | 1/8 (12.5%) | 1 |
| Surgical and medical procedures | ||
| Increased Bleeding from Biopsy Site | 1/8 (12.5%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Rodica Pop-Busui, MD, PhD |
|---|---|
| Organization | The University of Michigan |
| Phone | 734-763-3056 |
| rpbusui@umich.edu |
- SALP