Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03842709 |
| Other study ID # |
18-592 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Early Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2019 |
| Est. completion date |
February 15, 2021 |
Study information
| Verified date |
April 2022 |
| Source |
University of New Mexico |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
