Capsaicin + Oxygen + Cold Stimuli for Headache

(PBS Trial)

Overseen By Mark Burish, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Cardiovascular diseases, Brain tumors, Epilepsy, others

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

Compensation: Varies

Number of Visits: Unknown

371 Participants Needed

Trial Summary

What is the purpose of this trial?

This study investigates molecular and physical biomarkers of headaches in order to better understand mechanisms of these diseases. There are 3 main parts: 1. Use of capsaicin (active ingredient in hot chili peppers) to trigger release of calcitonin gene related peptide - the hypothesis is that this will be different in headache subjects compared to controls (and if so might be used to predict how these patients will respond to certain medications that modulate calcitonin gene-related peptide). Subjects will be given capsaicin as a cream applied to the forehead or the inner nostril, or a hot sauce that is ingested. 2. Use of capsaicin to trigger eye watering - the hypothesis is that oxygen gas will slow down the amount of eye watering. Cluster headache patients respond very powerfully to oxygen gas but to very little else. The mechanism for oxygen is unknown but in rodents there is data that it works on the parasympathetic / lacrimal gland system. This study translates rodent data into humans in a non-invasive way to confirm the mechanism of this very effective treatment. 3. Use of ice water to trigger headaches - brain freeze causes a very short-lived but intense headache that may cause similar biomarker release as other headache disorders. This may be a useful human model for other headache disorders.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it is best to discuss your specific situation with the trial coordinators.

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 study team or your doctor.

What data supports the idea that Capsaicin + Oxygen + Cold Stimuli for Headache is an effective treatment?

The available research shows that oxygen therapy is effective for treating cluster headaches, which are a type of severe headache. Studies have found that using high-flow oxygen can provide quick relief for many patients. For example, one study found that 68% of patients experienced pain relief after 30 minutes of using a demand valve oxygen mask. This suggests that oxygen therapy is a strong option for treating headaches. However, there is no specific data in the provided research about the combination of capsaicin, oxygen, and cold stimuli for headaches, so it's unclear how effective this specific combination is compared to just using oxygen therapy alone. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Capsaicin + Oxygen + Cold Stimuli for Headache?

Research shows that high-flow oxygen therapy is effective in treating cluster headaches, providing pain relief and reducing the need for additional medication. This suggests that oxygen therapy, as part of the combined treatment, may help alleviate headache symptoms. ^{1 2 3 4 5}

What safety data exists for the treatment of capsaicin, oxygen, and cold stimuli for headaches?

The safety data for the components of this treatment are as follows: High-flow oxygen therapy is widely used for cluster headaches and is considered effective with no treatment-related adverse events reported in studies. Capsaicin, particularly the 8% topical patch (Qutenza), has been shown to be effective for pain relief in postherpetic neuralgia with common side effects including application site erythema and pain. Systemic absorption is low, but some patients may experience transient increases in blood pressure. No specific safety data for cold stimuli in headache treatment is provided in the research. ^{1 2 3 5 6}

Is the combination of capsaicin and oxygen therapy safe for treating headaches?

Oxygen therapy has been used safely for cluster headaches, with no treatment-related adverse events observed in studies. Capsaicin patches, like Qutenza, are generally safe but can cause redness and pain at the application site, and sometimes a temporary increase in blood pressure. Both treatments have been studied for other conditions and are considered safe when used as directed. ^{1 2 3 5 6}

Is the treatment Capsaicin + Oxygen + Cold Stimuli for Headache promising?

Yes, the treatment is promising because oxygen therapy has been shown to be effective in relieving pain from cluster headaches, and it is recommended for patients who have frequent attacks or cannot tolerate drugs. ^{1 2 5 7 8}

How does the Capsaicin + Oxygen + Cold Stimuli treatment for headaches differ from other treatments?

This treatment is unique because it combines capsaicin, which is known for its pain-relieving properties, with oxygen therapy and cold stimuli, potentially offering a multi-faceted approach to headache relief. Oxygen therapy is already a standard treatment for cluster headaches, but the addition of capsaicin and cold stimuli may enhance its effectiveness by targeting different pain pathways. ^{1 2 5 7 8}

Research Team

Mark Burish MD PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

This trial is for adults who have been diagnosed with various headache disorders, including migraines and cluster headaches. They must be able to share medical records and not have a history of serious cardiovascular or neurovascular diseases, brain tumors, epilepsy, or be pregnant. Smokers and those with a life expectancy less than 1 year are excluded.

Inclusion Criteria

I have been diagnosed with a type of primary headache, such as migraine or tension headache.

I have been diagnosed with lumbar radiculopathy by a pain specialist.

The individual is able to provide authorization to share their prior medical records and imaging with healthcare providers.

Exclusion Criteria

You smoke or use tobacco or nicotine every day.

Active pregnancy or lactation

Active drug/alcohol use or dependence that would interfere with adherence to study requirements

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Capsaicin Application

Participants receive capsaicin in various forms (cream, nasal, oral) to trigger biomarker release

1 day per intervention

Multiple visits for different interventions

Oxygen and Eye Watering

Participants receive oxygen gas to assess its effect on eye watering triggered by capsaicin

1 day per intervention

Multiple visits for different interventions

Ice Water Application

Participants undergo ice water application to trigger headaches and assess biomarker release

1 day per intervention

Multiple visits for different interventions

Follow-up

Participants are monitored for safety and effectiveness after interventions

4 weeks

Treatment Details

Interventions

• Brain Freeze
• Cold Water Irrigation
• High Flow Oxygen
• Intranasal Capsaicin
• Low Flow Oxygen
• Medical Air
• Oral Capsaicin
• Topical Capsaicin

Trial Overview The study tests if capsaicin (from chili peppers) affects biomarkers in headache sufferers differently from controls when applied as cream, ingested, or used intranasally. It also examines if oxygen gas can reduce eye watering triggered by capsaicin and if ice water can simulate headaches to understand underlying mechanisms.

Participant Groups

Group I: Topical capsaicin and Low Flow Oxygen Experimental Treatment 2 Interventions

Group II: Topical capsaicin and High Flow Oxygen Experimental Treatment 2 Interventions

Group III: Topical capsaicin Experimental Treatment 1 Intervention

Group IV: Oral capsaicin and High Flow Oxygen Experimental Treatment 2 Interventions

Group V: Oral capsaicin Experimental Treatment 1 Intervention

Group VI: Oral Capsaicin and Low Flow Oxygen Experimental Treatment 2 Interventions

Group VII: Intranasal capsaicin and Low Flow Oxygen Experimental Treatment 2 Interventions

Group VIII: Intranasal capsaicin and High Flow Oxygen Experimental Treatment 2 Interventions

Group IX: Intranasal capsaicin Experimental Treatment 1 Intervention

Group X: Cold water irrigation and Low Flow Oxygen Experimental Treatment 2 Interventions

Group XI: Cold water irrigation and High Flow Oxygen Experimental Treatment 2 Interventions

Group XII: Cold water irrigation Experimental Treatment 1 Intervention

Group XIII: Intranasal capsaicin and Medical Air Placebo Group 2 Interventions

Group XIV: Topical capsaicin and Medical Air Placebo Group 2 Interventions

Group XV: Cold water irrigation and Medical Air Placebo Group 2 Interventions

Group XVI: Oral capsaicin and Medical Air Placebo Group 2 Interventions

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Findings from Research

In a study involving 57 cluster headache patients, the use of demand valve oxygen (DVO) showed a significant preference among patients and was more effective in achieving pain relief during the first attack compared to other mask types.

While the primary endpoint of pain relief at 15 minutes was not statistically significant, both DVO and O2ptimask reduced the need for rescue medication, suggesting they are effective options for acute treatment of cluster headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen therapy for cluster headache. A mask comparison trial. A single-blinded, placebo-controlled, crossover study. Petersen, AS., Barloese, MC., Lund, NL., et al.[2017]

High-flow oxygen inhalation is an effective acute treatment for cluster headaches, showing advantages over other medications since its introduction in 1952.

The exact mechanism of action is not fully understood, but it is believed to be linked to the trigeminovascular system and neuroinflammation, making it a preferred option for patients who experience frequent attacks or cannot tolerate other drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of oxygen in cluster headache. Guo, XN., Lu, JJ., Ni, JQ., et al.[2021]

Inhaled normobaric oxygen is an effective abortive treatment for cluster headaches, with its efficacy recognized for over 50 years, yet it has been under-discussed in the literature.

The article draws on data from the largest study of cluster headache patients, the United States Cluster Headache Survey, highlighting the importance of inhaled oxygen in a broad, real-world population rather than just clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled Oxygen for Cluster Headache: Efficacy, Mechanism of Action, Utilization, and Economics. Rozen, TD.[2021]

In a clinical trial involving 136 adult patients with moderate to severe primary headaches, the use of a non-rebreather mask (NRB) delivering oxygen at 15 l/min showed the most significant pain reduction at 30 minutes compared to other oxygen delivery methods.

However, the pain relief effect of the NRB method diminished by 60 minutes, indicating that while it may provide quick relief, it does not sustain significant pain reduction over a longer period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the effects of 3 oxygen delivery methods plus intravenous ketorolac on primary headaches: A randomized clinical trial. Saeedi, M., Shahvaran, SM., Ramezani, M., et al.[2020]

Oxygen therapy (OT) is an effective acute treatment for cluster headaches, with inhalation of 100% oxygen at flow rates of 6-12 L/min for 15-30 minutes being standard, although higher flow rates up to 15 L/min may provide even better relief.

While OT has shown efficacy in treating cluster headaches and some evidence in migraines, challenges in obtaining consistent results arise from varying inhalation protocols and small sample sizes in studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen Therapy in Cluster Headache, Migraine, and Other Headache Disorders. Mo, H., Chung, SJ., Rozen, TD., et al.[2022]

Qutenza, a high-potency capsaicin patch, significantly reduces pain associated with postherpetic neuralgia (PHN), showing a 29.6% to 32% reduction in pain compared to a control patch, with effects lasting up to 12 weeks.

The most common side effects include application site erythema (63%) and pain (42%), and it must be administered by a physician, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capsaicin 8% topical patch (Qutenza)--a review of the evidence. Jones, VM., Moore, KA., Peterson, DM.[2013]

In a study of 16 patients with cluster headaches, hyperbaric oxygen (HBO) treatment did not show a significant advantage over a placebo treatment in reducing headache severity or frequency, indicating that the hyperbaric condition itself may not be an effective intervention for chronic cluster headaches.

Despite the lack of difference in headache index between HBO and sham treatments, a notable 83% of episodic cluster headache patients and 25% of chronic patients experienced at least a 50% reduction in headache severity, suggesting a strong placebo effect or individual variability in response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen treatment of active cluster headache: a double-blind placebo-controlled cross-over study. Nilsson Remahl, AI., Ansjön, R., Lind, F., et al.[2017]

In a study involving 14 patients with chronic cluster headache, hyperbaric oxygen (HBO2) treatment showed clinical effectiveness, while the placebo group showed no changes in headache frequency or medication use.

The HBO2 treatment appeared to influence serotonergic pathways, as indicated by changes in serotonin binding to mononuclear cells, suggesting a potential mechanism of action for alleviating cluster headache symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen in chronic cluster headaches: influence on serotonergic pathways. Di Sabato, F., Rocco, M., Martelletti, P., et al.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Oxygen therapy for cluster headache. A mask comparison trial. A single-blinded, placebo-controlled, crossover study. [2017]

2. Australia pubmed.ncbi.nlm.nih.gov

The role of oxygen in cluster headache. [2021]

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

Inhaled Oxygen for Cluster Headache: Efficacy, Mechanism of Action, Utilization, and Economics. [2021]

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

Comparing the effects of 3 oxygen delivery methods plus intravenous ketorolac on primary headaches: A randomized clinical trial. [2020]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Oxygen Therapy in Cluster Headache, Migraine, and Other Headache Disorders. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Capsaicin 8% topical patch (Qutenza)--a review of the evidence. [2013]

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

Hyperbaric oxygen treatment of active cluster headache: a double-blind placebo-controlled cross-over study. [2017]

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

Hyperbaric oxygen in chronic cluster headaches: influence on serotonergic pathways. [2013]