DPA-714 PET/MRI for Chronic Pain and Fatigue

(DPA-714 Trial)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Alabama at Birmingham

Disqualifiers: Pregnancy, Cancer, Autoimmune, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial uses a special imaging test to look for brain inflammation in people with chronic pain and fatigue. The test works by highlighting inflamed areas in the brain, helping researchers see if these patients have more brain inflammation compared to healthy individuals.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What evidence supports the effectiveness of the drug DPA-714 PET/MRI for chronic pain and fatigue?

Research on similar treatments, like adenosine A1 receptor partial agonists, shows they can reduce pain in neuropathic conditions by acting on specific receptors in the body. Additionally, positive allosteric modulators of certain receptors have shown potential in reducing pain in animal models, suggesting that targeting these pathways could be effective for managing chronic pain. ^{1 2 3 4 5}

Is DPA-714 PET/MRI safe for humans?

The available research does not provide specific safety data for DPA-714 PET/MRI in humans, but it has been used as a radioligand for imaging in studies, suggesting it is generally considered safe for such purposes. ^{6 7 8 9 10}

What makes the drug DPA-714 PET/MRI unique for chronic pain and fatigue?

DPA-714 PET/MRI is unique because it uses a radioligand that targets the translocator protein (TSPO), which is associated with neuroinflammation, allowing for detailed imaging of microglial activation in the brain. This approach provides a non-invasive way to study and potentially diagnose conditions related to chronic pain and fatigue by visualizing inflammation in the central nervous system. ^{8 10 11 12 13}

Research Team

Eligibility Criteria

This trial is for adults aged 18-65 who are healthy or have a diagnosis of Multiple Sclerosis, meet criteria for fibromyalgia or Chronic Fatigue Syndrome. It's not suitable for pregnant or lactating individuals, those with MRI contraindications, severe medical conditions preventing imaging participation, chronic infections like HIV/HCV, recent acute illness requiring antibiotics, cancer diagnoses, blood disorders, autoimmune diseases (except MS), or current involvement in trials with experimental therapies.

Inclusion Criteria

I am healthy or have MS, fibromyalgia, or Chronic Fatigue Syndrome.

I am between 18 and 65 years old.

Exclusion Criteria

Currently enrolled in a clinical trial utilizing experimental therapies

You are currently breastfeeding.

You cannot have an MRI for medical reasons.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo PET/MRI imaging to measure neuroinflammation using [F-18]DPA-714

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

Treatment Details

Interventions

• DPA-714 PET/MRI (PET Radiopharmaceutical)

Trial Overview The study tests how a PET radiopharmaceutical called [F-18]DPA-714 maps brain inflammation in patients with chronic pain and fatigue versus healthy controls. The drug binds to specific proteins in activated immune cells within the brain to visualize neuroinflammation using PET/MRI technology.

Participant Groups

Group I: Multiple Sclerosis Subjects Experimental Treatment 1 Intervention

Group II: Healthy Controls Experimental Treatment 1 Intervention

Group III: Fibromyalgia Subjects Experimental Treatment 1 Intervention

Group IV: Chronic Fatigue Syndrome Subjets Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Kierstin Kennedy

University of Alabama at Birmingham

Chief Medical Officer since 2022

MD

S. Dawn Bulgarella

University of Alabama at Birmingham

Chief Executive Officer since 2023

BSc in Commerce and Business Administration from the University of Alabama, MS in Health Administration from the University of Alabama at Birmingham

Findings from Research

Adenosine A1 receptor partial agonists, specifically MCPA and 2'dCPA, demonstrated a full anti-hyperalgesic effect in a neuropathic pain model, indicating their potential effectiveness in reducing pain sensitivity.

While these partial agonists showed strong anti-hyperalgesic effects, their anti-nociceptive effects were significantly lower compared to a full agonist, suggesting that while they can alleviate certain pain symptoms, they may not be as effective in blocking pain signals overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/pharmacodynamic modelling of the anti-hyperalgesic and anti-nociceptive effect of adenosine A1 receptor partial agonists in neuropathic pain. Schaddelee, MP., Collins, SD., DeJongh, J., et al.[2013]

A new compound, 1t, was developed as a positive allosteric modulator (PAM) of the MRGPRX1 receptor, showing potential for treating neuropathic pain by preferentially activating receptors in the spinal cord after oral administration.

In a neuropathic pain model, compound 1t significantly reduced heat hypersensitivity in mice, indicating its efficacy and therapeutic potential for pain management without the common side effects associated with peripheral receptor activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thieno[2,3-d]pyrimidine-Based Positive Allosteric Modulators of Human Mas-Related G Protein-Coupled Receptor X1 (MRGPRX1). Berhane, I., Hin, N., Thomas, AG., et al.[2023]

5'-deoxy-N6-cyclopentyl-adenosine (5'dCPA) shows a significant anti-hyperalgesic effect in a neuropathic pain model, with an effective concentration (EC50) of 178 ng/ml, indicating its potential as a treatment for pain relief.

The study suggests that high plasma concentrations of 5'dCPA are necessary for its effectiveness, which may be due to limited transport to the spinal cord or brain, highlighting a challenge in its therapeutic application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic-pharmacodynamic modelling of the anti-hyperalgesic effect of 5'deoxy-N6-cylopentyladenosine in the mononeuropathic rat. Schaddelee, MP., Dejongh, J., Collins, SD., et al.[2013]

The new compound (S)-17 (UCM-05194) is identified as the most potent and selective agonist for the LPA1 receptor, showing significant efficacy in reducing neuropathic pain in an in vivo model.

By activating the LPA1 receptor, (S)-17 induces internalization of the receptor, leading to its functional inactivation in sensory neurons, which contributes to its ability to attenuate pain perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration. González-Gil, I., Zian, D., Vázquez-Villa, H., et al.[2021]

The English version of the Würzburg Fabry Pain Questionnaire (enFPQ) was successfully validated for self-administration in 83 adult patients with Fabry disease, demonstrating high agreement between supervised and self-reported pain assessments.

The enFPQ effectively captures detailed information about the unique pain characteristics of Fabry disease, which can enhance pain classification and improve treatment strategies for affected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

English version of the self-administered Fabry Pain Questionnaire for adult patients. Jovanovic, A., Klassen, P., Heuschmann, P., et al.[2021]

The study evaluated the binding of the radioligand 18F-DPA-714 in both healthy subjects and Alzheimer's disease patients, using advanced PET imaging techniques to generate quantitative images of its distribution.

Both plasma-input Logan analysis and spectral analysis were found to be effective methods for producing accurate images of 18F-DPA-714 binding, which could aid in further research and voxel-based comparisons in neuroimaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parametric Binding Images of the TSPO Ligand 18F-DPA-714. Golla, SS., Boellaard, R., Oikonen, V., et al.[2017]

Four new analogues of DPA-714 were developed, showing improved affinity and selectivity for the TSPO receptor compared to the original compound, indicating potential for enhanced therapeutic effects.

The selected analogue, DPA-C5yne, demonstrated favorable metabolic stability and was successfully labeled with fluorine-18 for PET imaging, suggesting its utility in studying neuroinflammation in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preparation and evaluation of novel pyrazolo[1,5-a]pyrimidine acetamides, closely related to DPA-714, as potent ligands for imaging the TSPO 18kDa with PET. Médran-Navarrete, V., Damont, A., Peyronneau, MA., et al.[2016]

DPA-714 is a newly developed radioligand for imaging microglia activation and neuroinflammation using positron emission tomography (PET), providing a valuable tool for studying these processes in vivo.

The creation of a tritium-labeled version of DPA-714 allows for high-resolution imaging and detailed pharmacokinetic studies, enhancing our understanding of its binding properties and potential applications in neuroinflammatory research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficient tritiation of the translocator protein (18 kDa) selective ligand DPA-714. Damont, A., Garcia-Argote, S., Buisson, DA., et al.[2015]

A new series of fluorinated analogues of the TSPO ligand CfO-DPA-714 were developed, showing high affinity and selectivity for the TSPO, with some compounds demonstrating better binding than the original DPA-714.

One promising compound, an N-methyl-N-propyl amide analogue, exhibited similar metabolic stability to CfO-DPA-714 and could be a strong candidate for use as a PET imaging probe for neuroinflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and in vitro characterization of novel fluorinated derivatives of the translocator protein 18 kDa ligand CfO-DPA-714. Cacheux, F., Médran-Navarrete, V., Dollé, F., et al.[2017]

The new radioligand [11C]DPA-713 shows improved radiochemical yield (30-38%) and simpler purification methods compared to previous methods, making it more efficient for use in studies of peripheral benzodiazepine receptors.

The synthesis process for [11C]DPA-713 takes only 18-20 minutes, which enhances its suitability for automated production and repeated use in pharmacological and clinical evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved synthesis of the peripheral benzodiazepine receptor ligand [11C]DPA-713 using [11C]methyl triflate. Thominiaux, C., Dollé, F., James, ML., et al.[2006]

The new radiotracer [18F]F-DPA was successfully synthesized and showed a high radiochemical purity of over 99%, indicating its potential for reliable use in imaging neuroinflammation.

In comparison to the related radiotracer [18F]DPA-714, [18F]F-DPA demonstrated a significantly higher stability in vivo, with 93.5% of the radioactivity remaining unchanged in the brain, suggesting it may be more effective for imaging neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosynthesis and Preclinical Evaluation of [18F]F-DPA, A Novel Pyrazolo[1,5a]pyrimidine Acetamide TSPO Radioligand, in Healthy Sprague Dawley Rats. Keller, T., Krzyczmonik, A., Forsback, S., et al.[2023]

DPA-C5yne is a highly selective and high-affinity ligand for the translocator protein 18 kDa, with a binding affinity of 0.35 nM, indicating its potential as a targeted therapeutic agent.

The compound can be efficiently labeled with fluorine-18 for use in PET imaging, yielding a high purity and specific radioactivity, and it remains stable in plasma for at least 90 minutes, suggesting good safety and efficacy for in vivo applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]DPA-C5yne, a novel fluorine-18-labelled analogue of DPA-714: radiosynthesis and preliminary evaluation as a radiotracer for imaging neuroinflammation with PET. Médran-Navarrete, V., Bernards, N., Kuhnast, B., et al.[2016]

This case study demonstrates that 18F-florbetapir PET/MRI can effectively measure myelin recovery in a patient with GFAP astrocytopathy, indicating significant demyelination and subsequent recovery after treatment.

The use of this imaging technique not only showed increased tracer uptake in brain lesions post-treatment but also correlated with improved clinical outcomes, suggesting its potential for early diagnosis and better long-term prognosis in GFAP-A patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hybrid 18F-florbetapir PET/MRI for assessing myelin recovery in GFAP-A patients. Meng, H., Zheng, S., Yuan, S., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/pharmacodynamic modelling of the anti-hyperalgesic and anti-nociceptive effect of adenosine A1 receptor partial agonists in neuropathic pain. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Thieno[2,3-d]pyrimidine-Based Positive Allosteric Modulators of Human Mas-Related G Protein-Coupled Receptor X1 (MRGPRX1). [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic-pharmacodynamic modelling of the anti-hyperalgesic effect of 5'deoxy-N6-cylopentyladenosine in the mononeuropathic rat. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration. [2021]

5. England pubmed.ncbi.nlm.nih.gov

English version of the self-administered Fabry Pain Questionnaire for adult patients. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Parametric Binding Images of the TSPO Ligand 18F-DPA-714. [2017]

7. England pubmed.ncbi.nlm.nih.gov

Preparation and evaluation of novel pyrazolo[1,5-a]pyrimidine acetamides, closely related to DPA-714, as potent ligands for imaging the TSPO 18kDa with PET. [2016]

8. England pubmed.ncbi.nlm.nih.gov

Efficient tritiation of the translocator protein (18 kDa) selective ligand DPA-714. [2015]

9. France pubmed.ncbi.nlm.nih.gov

Synthesis and in vitro characterization of novel fluorinated derivatives of the translocator protein 18 kDa ligand CfO-DPA-714. [2017]

10. England pubmed.ncbi.nlm.nih.gov

Improved synthesis of the peripheral benzodiazepine receptor ligand [11C]DPA-713 using [11C]methyl triflate. [2006]

11. United States pubmed.ncbi.nlm.nih.gov

Radiosynthesis and Preclinical Evaluation of [18F]F-DPA, A Novel Pyrazolo[1,5a]pyrimidine Acetamide TSPO Radioligand, in Healthy Sprague Dawley Rats. [2023]

12. England pubmed.ncbi.nlm.nih.gov

[18F]DPA-C5yne, a novel fluorine-18-labelled analogue of DPA-714: radiosynthesis and preliminary evaluation as a radiotracer for imaging neuroinflammation with PET. [2016]

13. Germany pubmed.ncbi.nlm.nih.gov

Hybrid 18F-florbetapir PET/MRI for assessing myelin recovery in GFAP-A patients. [2022]