Non-Opioid Pramipexole and Pain

• Status: Unknown status
• Trial end date: 2020-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The long-term goal of this proposal is to identify non-opioid drugs that harness endogenous anti-inflammatory mechanisms resulting in the suppression of proinflammatory cytokines such as IL-1ß providing a novel approach to treat chronic pain in people while lacking potential for addictive side effects.

Specific Aim I: pramipexole blocks the activation of NLRP3 and consequent production and release of the proinflammatory cytokines IL-1ß, IL-6 and TNF-α, and increases production of the anti-inflammatory cytokine interleukin-10 (IL-10).

The goal of Aim I (Phase I) experiments is to examine the specific anti-inflammatory mechanisms of pramipexole on PAMP, DAMP and opioid stimulated immune cells, THP-1 cells will be used.

Specific Aim II: pramipexole treatment will provide therapeutic benefit to patients experiencing suboptimal pain relief from current standard therapy with concurrent reduction of TLR4-NLRP3-cytokine expression in peripheral blood mononuclear cells.

The goal of Aim II (Phase II) will be to determine the therapeutic benefit of pramipexole for pain, which is a repurposing of this FDA-approved drug with a good safety profile.

1.2. Our overarching hypothesis is that pramipexole will control clinical pain by suppressing the activation of the TLR4-NLRP3-IL-1ß pathway and prevent IL-1ß release from peripheral immune cells. These findings have provided the current impetus to examine pain therapeutic drugs targeting immune-related factors either upstream or downstream of IL-1ß signaling.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of New Mexico
• Collaborator: University of New Mexico Clinical and Translational Science Center
• Treatments: Analgesics, Non-Narcotic; Pramipexole

Criteria

Inclusion Criteria:

• Nonmalignant chronic pain patients at University of New Mexico Pain Clinic, reporting suboptimal pain control, who state an interest to try something new to improve pain relief

• Pain score of 5 or greater (0-10 scale)

• Pain lasting more than 3 months

Exclusion Criteria:

• Patients who do not speak English or Spanish

• Patients unable to consent

• Women who are not post-menopausal, or who have not undergone an oophorectomy/hysterectomy

• Patients who have chronic pulmonary, kidney or liver disease

• Patients with a body mass index (BMI) ≥35

• Patients with a cancer diagnosis within the last 2 years (except non-melanoma skin cancer)

• Patients who are currently lactating

• Patients with a history of orthostatic hypotension

• Patients diagnosed with a dissociative disorder

• Patients with Parkinson's disease, and/or currently taking dopamine agonist prescription medications

• Prisoners and other institutionalized individuals