Targeting Inflammation With Salsalate in Type 1 Diabetes Neuropathy (TINSAL-T1DN)
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|ClinicalTrials.gov Identifier: NCT02936843|
Recruitment Status : Recruiting
First Posted : October 18, 2016
Last Update Posted : December 4, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Type 1 Diabetes Peripheral Neuropathy||Drug: Salsalate Drug: PLACEBO||Phase 2 Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Targeting Inflammation With Salsalate in Type 1 Diabetes Neuropathy-TINSAL -T1DN|
|Study Start Date :||October 2016|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||June 2023|
Salsalate, 1 gram by mouth, 3 times daily (3 grams per day) for 12 months.
1 gram, 3 times daily by mouth (total of 3 grams daily)
Other Name: disalcid
Placebo Comparator: Comparator
Placebo for Salsalate, 2 tablets by mouth, 3 times daily for 12 months
Placebo for Salsalate; 2 Tabets, 3 times daily by mouth (total of 3 grams daily)
- Skin Biopsy - Intraepidermal Nerve Fiber Density (IENFD) - Distal Thigh [ Time Frame: 12 months ]Change from baseline to month 12 in the intraepidermal nerve fiber density. 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 subjects with and without neuropathy. The morphometric quantification of IENFD, most commonly expressed as the number of IENFs per length of section (IENF/mm e.g. density) is possible with skin biopsy (IENFD) at the distal thigh.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02936843
|Contact: Rodica Pop-Busui, MD, PhDfirstname.lastname@example.org|
|Contact: Jacob Reiss, BSemail@example.com|
|United States, Michigan|
|University of Michigan Health System||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Abby Burant, BS 734-615-0552 firstname.lastname@example.org|
|Contact: Jacob Reiss, BS 734-763-0177 email@example.com|
|Principal Investigator: Rodica Pop-Busui, MD, PhD|
|Sub-Investigator: Lynn Ang, MD|
|Principal Investigator: Eva Feldman, MD, PhD|
|Sub-Investigator: Kara Mizukami-Stout, MD|
|Henry Ford Health System||Recruiting|
|Detroit, Michigan, United States, 48202|
|Contact: Liz Warner 313-916-3608 firstname.lastname@example.org|
|Contact: Heather Remtema, MPH 313-916-3906 email@example.com|
|Principal Investigator: Davida F Kruger, MSN, APN-BC, BC-ADM|
|Principal Investigator:||Rodica Pop-Busui, MD, PhD||University of Michigan|