Topics

Non-Opioid Pramipexole and Pain

2019-02-20 23:09:17 | BioPortfolio

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.

Description

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.

This study is conducted to determine the therapeutic benefit of pramipexole for pain, which is a repurposing of this FDA-approved drug with a good safety profile. In collaboration with Dr. Koshkin (co-I at UNMH Pain Clinic), patients from the UNM pain clinic will be recruited who are experiencing modest or suboptimal pain relief. The patient will meet the CTSC Clinical Research Coordinator, who will escort the patient to the Clinical Research Lab. At the time, an explanation of the study, consent, the Brief Pain Inventory survey will be completed, blood draw and Clincard will be given to the patient ($15/visit). Scheduling for the midterm visit to the CTSC (at the end of two weeks) will be determined. At the time of consent, all patients will be under standard pain treatment and will be randomized into two groups: (1) patients receiving pramipexole in addition to their standard ongoing pain treatment, or (2) no pramipexole but will continue to receive the standard pain treatment. Patients will be followed up in the morning at weekly intervals to provide pain scores either by phone (for week 1 and 3), or by return visit (for end of week 2 and at the end of week 4) until study termination which is at the end of week 4.. At the initiation of the study and at the end of 4 weeks, blood will be collected and analyzed for mRNA for TLR4, p38, NFkB, NLRP3-ASC, Caspase-1, IL-1ß, TNF-α, HMGB1, and IL-10. The dose and route of administration of pramipexole will be identical to that previously approved for the treatment of Restless Legs Syndrome and according to manufacturer's recommended prescribing protocol (Mirapex, Boehringer Ingelheim Int. GmbH). Briefly, oral dosage will be titrated each week to achieve a weekly total daily dose of 0.125 (mg), 0.250, or 0.5. Patients will take one capsule containing pramipexole of placebo 2-3 hours before bedtime.

Patient recruitment, assessment of Brief Pain Inventory (BPI): Pain scores and blood draws will be conducted at the CTSC Participant Clinical Interactions Unit with the CTSC Clinical Research Coordinator. Blood samples collected by the CTSC Clinical Research Coordinator will be analyzed at the Center for Molecular Discovery by personnel from Dr. Milligan's lab, trained by personnel from the Center for Molecular Drug Discovery (Director; Dr. Sklar, co-I). Personnel from the Milligan lab have expertise in inflammatory marker analysis from PBMCs [57, 58]. All freshly collected blood samples will be frozen and stored by the Clinical Research Coordinator at the CTSC Clinical Laboratory and will be transported to the Center for Molecular Drug Discovery once ALL of the samples for the study have been collected for mRNA and protein analysis. This is to allow for assay to be conducted at the same time to avoid potential effect of 'time of assay' that may impact data.

All subjects will therefore meet with the CTSC Clinical Research Coordinator for a total of 3 times; at the initiation of the study, at mid-term when the second batch of drug is dispensed and unused drug is returned, and at termination for a second and final blood draw and providing all completed Brief Pain Inventory surveys (4/patient). At the termination of the study, patients will turn in their paper copies of the Brief Pain Inventory questionnaire completed for each week of the study (total 4 weeks). Original data records are important to demonstrate all necessary physical documentation of the study.

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.

Study Design

Conditions

Chronic Pain

Intervention

Pramipexole Oral Tablet, Placebo

Location

University of New Mexico Hospital
Albuquerque
New Mexico
United States
87131

Status

Not yet recruiting

Source

University of New Mexico

Results (where available)

View Results

Links

Published on BioPortfolio: 2019-02-20T23:09:17-0500

Clinical Trials [6613 Associated Clinical Trials listed on BioPortfolio]

A Randomized, Double-blind, Active (Pramipexole 0.5 mg Tid) and Placebo Controlled, Study of Pramipexole Given 0.5 mg and 0.75 mg Bid Over 12-week Treatment in Early PD Patients

Primary objective: to assess the efficacy of pramipexole given two times daily compared to placebo. Secondary objectives: to assess the effects of pramipexole on mood, cognition, fatigue,...

Effect of Pre-medication in Pain Measures on Office Hysteroscopy

Will be perform a RCT to compare pain measure on office hysteroscopy after pre-medication with oral analgesic. Patients will be alocate to oral sodic diclofenac, scopolamin or placebo. We ...

Long-term Safety Study of Open-label Pramipexole ER in Patients With Advanced PD

The general aim of this study is to obtain long-term safety and tolerability data on pramipexole ER, in daily doses from 0.375mg to 4.5mg qd, in patients who have previously completed a pr...

Pramipexole Dihydrochloride 0.25 mg Tablets Under Fasting Conditions

The object of this study was to compare the relative bioavailability (rate and extent of absorption) of Pramipexole Dihydrochloride Tablets 0.25 mg by Barr Laboratories, Inc. with that of ...

Pramipexole Dihydrochloride 0.25 mg Tablets Under Non-Fasting Conditions

The object of this study was to compare the relative bioavailability (rate and extent of absorption) of Pramipexole Dihydrochloride Tablets 0.25 mg by Barr Laboratories, Inc. with that of ...

PubMed Articles [14330 Associated PubMed Articles listed on BioPortfolio]

Efficacy of Chewing Gum to Reduce Orthodontic Pain Compared to Placebo: A Blinded, Parallel-Group, Preliminary Clinical Trial.

To quantify the pain experienced by orthodontic patients during the first 10 days of appliance placement, to determine whether chewing gum reduces orthodontic pain compared to placebo, and to examine ...

Percutaneous peripheral nerve stimulation for the treatment of chronic neuropathic postamputation pain: a multicenter, randomized, placebo-controlled trial.

Chronic neuropathic pain is a common challenging condition following amputation. Recent research demonstrated the feasibility of percutaneously implanting fine-wire coiled peripheral nerve stimulation...

Neurotransmitter systems involved in placebo and nocebo effects in healthy participants and patients with chronic pain: a systematic review.

The investigation of neurotransmitter systems in placebo and nocebo effects has improved our understanding of these phenomena. Yet, the majority of studies involve healthy participants. As the pain mo...

Ropivacaine versus placebo on postoperative analgesia and chronic pain following third molar extraction: a prospective randomized controlled study.

The present study aimed at assessing the efficiency of ropivacaine on post-operative pain for extraction of third molars.

Endogenous Pain Modulation Assessed with Offset Analgesia Is Not impaired in Chronic Temporomandibular Disorders Pain Patients.

Abnormal endogenous pain modulation (EPM) was suggested as a pathophysiological characteristic of chronic pain. EPM has been investigated using psychophysical tests for pain facilitation and inhibitio...

Medical and Biotech [MESH] Definitions

Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous SPRAINS AND STRAINS; INTERVERTEBRAL DISK DISPLACEMENT; and other conditions.

Facilities providing diagnostic, therapeutic, and palliative services for patients with severe chronic pain. These may be free-standing clinics or hospital-based and serve ambulatory or inpatient populations. The approach is usually multidisciplinary. These clinics are often referred to as "acute pain services". (From Br Med Bull 1991 Jul;47(3):762-85)

An acute or chronic GINGIVITIS characterized by redness and swelling, NECROSIS extending from the interdental papillae along the gingival margins, PAIN; HEMORRHAGE, necrotic odor, and often a pseudomembrane. The condition may extend to the ORAL MUCOSA; TONGUE; PALATE; or PHARYNX. The etiology is somewhat unclear, but may involve a complex of FUSOBACTERIUM NUCLEATUM along with spirochetes BORRELIA or TREPONEMA.

Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain.

Acute or chronic pain located in the posterior regions of the THORAX; LUMBOSACRAL REGION; or the adjacent regions.

More From BioPortfolio on "Non-Opioid Pramipexole and Pain"

Quick Search

Relevant Topics

Biological Therapy
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...

Pain
Pain is defined by the International Association for the Study of Pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage”. Some illnesses can be excruci...

Cytokine Tumour Necrosis Factor (TNF)
TNF is a compound that is classified as a cytokine which plays a central role in the cellular mechanisms of apoptosis or cell death. However, there are a number of different kinds of TNF, just under twenty, but the family of molecules have very similar a...


Searches Linking to this Trial