DPA-714 PET/MRI for Chronic Pain and Fatigue

(DPA-714 Trial)

Overseen By Jonathan McConathy, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Disqualifiers: Pregnancy, Cancer, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the potential link between brain inflammation and chronic pain and fatigue using a special PET/MRI scan with a tracer called DPA-714. It seeks to determine whether individuals with conditions like fibromyalgia, chronic fatigue syndrome, or multiple sclerosis exhibit more brain inflammation than healthy individuals. Those diagnosed with one of these conditions and experiencing persistent pain or fatigue might be suitable candidates for the trial. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to contribute to groundbreaking insights.

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 prior data suggests that DPA-714 PET/MRI is safe for measuring neuroinflammation?

Research has shown that the [F-18]DPA-714 tracer used in PET/MRI scans measures brain inflammation by attaching to certain proteins in the brain. Although detailed safety information for this tracer in humans is not widely available, it has been used in studies for conditions like fibromyalgia and multiple sclerosis. These studies aim to observe inflammation, not treat it, using the tracer to provide important imaging information rather than therapeutic effects.

In early-stage trials, specific safety data might be limited, so researchers closely monitor how well participants tolerate the tracer. As this is a phase 1 study, the goal is to ensure safety and understand how the body responds to the tracer. Testing this tracer in humans suggests that earlier studies have deemed it safe enough for further research. Participation in a trial using this tracer would help researchers confirm its safety and contribute to important scientific knowledge about chronic pain and fatigue. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for chronic pain and fatigue, like medication and physical therapy, the DPA-714 PET/MRI technique offers a new way to understand these conditions. This method uses a special imaging agent, DPA-714, combined with PET/MRI scans to visualize inflammation in the brain, which could be a key factor in chronic pain and fatigue. Researchers are excited because this could lead to more targeted therapies, potentially transforming how conditions like fibromyalgia, chronic fatigue syndrome, and multiple sclerosis are diagnosed and treated.

What evidence suggests that DPA-714 PET/MRI is effective for measuring neuroinflammation in chronic pain and fatigue?

Research has shown that a special type of scan called DPA-714 PET/MRI holds promise for detecting brain inflammation in people with chronic pain and fatigue. This trial will include healthy controls, fibromyalgia subjects, chronic fatigue syndrome subjects, and multiple sclerosis subjects. One study found that people with fibromyalgia have more brain inflammation than healthy individuals, which might be a key reason for their pain and tiredness. Another study discovered inflammation in certain brain areas of people with multiple sclerosis. These findings suggest that DPA-714 PET/MRI can effectively identify inflammation, potentially aiding in understanding and managing these conditions. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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.

Exclusion Criteria

Currently enrolled in a clinical trial utilizing experimental therapies

You are currently breastfeeding.

You cannot have an MRI for medical reasons.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• DPA-714 PET/MRI

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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 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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10502894/

a [18F]DPA-714 positron emission tomography study - PMC This observational study aimed to determine whether individuals with fibromyalgia (FM) exhibit higher levels of neuroinflammation than healthy controls (HCs).

2. withpower.com withpower.com/trial/phase-1-fibromyalgia-1-2019-8437d

DPA-714 PET/MRI for Chronic Pain and Fatigue 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 ...

3. trials.arthritis.org trials.arthritis.org/trials/NCT03759522

Assessment of Neuroinflammation in Central Inflammatory ... The primary objective of this study is to determine if pain and fatigue patients have higher levels of neuroinflammation than HC individuals as measured with [F ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37039158/

Positron Emission Tomography with [18 F]-DPA-714 ... The [ 18 F]-DPA-714-PET revealed that an unexpectedly high proportion of MS lesions have a smoldering component, which predicts atrophy and clinical ...

5. researchgate.net researchgate.net/publication/371639715_Evidence_of_neuroinflammation_in_fibromyalgia_syndrome_a_18FDPA-714_positron_emission_tomography_study

Evidence of neuroinflammation in fibromyalgia syndrome Abstract. This observational study aimed to determine whether individuals with fibromyalgia (FM) exhibit higher levels of neuroinflammation.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06280742

Study of Neuroinflammation in Multiple Sclerosis by PET ... Recent findings from [18F]-DPA-714 PET imaging in MS patients revealed that most of the white matter lesions contained a smoldering component, even when ...

7. pubs.rsna.org pubs.rsna.org/doi/pdf/10.1148/radiol.230397

Microglial Activation Imaging Using 18F-DPA-714 PET/MRI ... Positron emission tomography with. [18F]-DPA-714 unveils a smoldering component in most multiple sclerosis lesions which drives disease ...