Chronic PainEarly Phase 1NCT03842709
Non-Opioid Pramipexole and Pain
A Early Phase 1 study testing Pramipexole Oral Tablet in people with Chronic Pain, run by University of New Mexico at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Pain
- What is being tested?
- Pramipexole Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2019to 15 Feb 2021
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of New Mexico Hospital
Albuquerque, New Mexico, 87131
About this study
Official title: Non-opioid Pramipexole Suppresses Immune NLRP3 Reactivity for Pain Control
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).
Read more
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.
Read the detailed 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.
- Conditions
- Chronic Pain
- Being tested
- Pramipexole Oral Tablet, Placebo
- Medical subject headings
- Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pramipexole Oral TabletDrug
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.
PlaceboOther
Administration of placebo
| Study group | Role | What they receive |
|---|---|---|
| Standard Treatment + Placebo | Placebo comparator | Patients reporting sub-optimal results of pain therapy, assigned to placebo in addition to routine care. Receives: Other: Placebo |
| Standard Treatment + Pramipexole | Experimental | Patients reporting sub-optimal results of pain therapy, assigned to receive pramipexole in addition to routine care. Receives: Drug: Pramipexole Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 weeks
Secondary outcomes (1)
mRNA Results IL-1b
Fold change of the mRNA gene expression from the house keeping gene and the controls.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2019
- Study start1 May 2019
- Primary completion31 Jan 2020
- Study completion15 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of New Mexico
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Erin Damita Milligan, University of New Mexico
- Investigators
- Erin D Milligan, PhD, Principal investigator, University of New Mexico Health Sciences Center (HSC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03842709
- Sponsor's protocol ID
- 18-592
- Status last verified
- Oct 2024
- First submitted
- 8 Feb 2019
- Last updated
- 23 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-opioid Pramipexole Suppresses Immune NLRP3 Reactivity for Pain Control
- ClinicalTrials.gov ID
- NCT03842709
- Acronym / sponsor ID
- 18-592
- Conditions
- Chronic Pain
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of New MexicoUniversity, hospital or other
- Study start
- 1 May 2019 (actual)
- Primary completion
- 31 Jan 2020 (actual)
- Study completion
- 15 Feb 2021 (actual)
- First posted
- 15 Feb 2019 (actual)
- Results
- Posted 23 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Treatment + Placebo | Placebo comparator | Other: PlaceboPatients reporting sub-optimal results of pain therapy, assigned to placebo in addition to routine care. |
| Standard Treatment + Pramipexole | Experimental | Drug: Pramipexole Oral TabletPatients reporting sub-optimal results of pain therapy, assigned to receive pramipexole in addition to routine care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pramipexole Oral TabletInitial 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. | Drug | Standard Treatment + Pramipexole |
| PlaceboAdministration of placebo | Other | Standard Treatment + Placebo |
Primary outcome
Brief Pain Inventory Score
Time frame: 4 weeks
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.
1 secondary outcome
mRNA Results IL-1b
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Erin D Milligan, PhD principal investigator
University of New Mexico Health Sciences Center (HSC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Pramipexole Oral Tablet in people with Chronic Pain, run by University of New Mexico at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brief Pain Inventory Score (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2024.