Non-Opioid Pramipexole and Pain

NCT03842709 | Completed Early Phase 1 Results FDA Drug

• 1 other identifier: 18-592
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Pain

Outcome Measures

Primary Outcomes (1)

• Brief Pain Inventory Score

  Change in self-reported effect of pain on quality of life. The "Brief Pain Inventory, Short Form," instrument will be used. It records severity (0-10 scale; 10= worst pain) at its worst.

  4 weeks

Secondary Outcomes (1)

• mRNA Results IL-1b

  4 weeks

Study Arms (2)

Standard Treatment + Placebo

PLACEBO COMPARATOR

Patients reporting sub-optimal results of pain therapy, assigned to placebo in addition to routine care.

Other: Placebo

Standard Treatment + Pramipexole

EXPERIMENTAL

Patients reporting sub-optimal results of pain therapy, assigned to receive pramipexole in addition to routine care.

Drug: Pramipexole Oral Tablet

Interventions

Pramipexole Oral Tablet DRUG

Initial dosage of 0.125 mg pramipexole daily, potentially titrated upward in 0.125 increments to a maximum of 0.5 mg daily, for 4 weeks.

Standard Treatment + Pramipexole

Placebo OTHER

Administration of placebo

Standard Treatment + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of New Mexico: lead

Study Sites (1)

University of New Mexico Hospital

Albuquerque, New Mexico, 87131, United States

Location

MeSH Terms

Conditions

Chronic Pain

Interventions

Pramipexole

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzothiazoles; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: ERIN MILLIGAN,
• Organization: University of New Mexico-Dept of Neurosciences

EMilligan@salud.unm.edu

505-272-4411

Study Officials

• Erin D Milligan, PhD

  University of New Mexico Health Sciences Center (HSC)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 8, 2019
• First Posted: February 15, 2019
• Study Start: May 1, 2019
• Primary Completion: January 31, 2020
• Study Completion: February 15, 2021
• Last Updated: October 23, 2024
• Results First Posted: October 23, 2024

Record last verified: 2024-10

Locations

US (1)