Mind and Body Approaches for Migraine

Overseen By LeighAnn Chamberlin, MEd

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must not be taking: Opioids, Antipsychotics, Benzodiazepines, others

Disqualifiers: Epilepsy, Neurological diseases, Psychiatric diseases, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different treatments to understand how young people with migraines respond to preventive care. It includes options like cognitive behavioral therapy (CBT), biofeedback-assisted relaxation training (BART), cognitive reappraisal (CR) training, and amitriptyline (a medication), compared against a placebo. The researchers aim to explore both mind and body approaches to assess their effects on brain function and pain management. The trial suits English-speaking youth who experience migraines 8 to 28 times a month and face daily life disruption due to headaches. Participants will keep headache diaries and undergo brain scans as part of the study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop certain medications. You cannot take prophylactic anti-migraine medication before the trial and must avoid starting any during the study. You also cannot use opioids, antipsychotics, antimanics, barbiturates, benzodiazepines, muscle relaxants, sedatives, tramadol, or nutraceuticals. Additionally, you must limit the use of NSAIDs to no more than 3 times per week and triptans to no more than 6 times per month.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications, such as NSAIDs more than 3 times a week, or migraine-specific medications like triptans more than 6 times a month. You also cannot be on any current migraine prevention medication or certain other medications like opioids, antipsychotics, or muscle relaxants during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have explored the safety of amitriptyline, one of the treatments being tested. Amitriptyline is already used for migraines and other types of pain. The doses for pain are lower than those for depression, resulting in milder side effects. Common side effects, such as drowsiness or dry mouth, usually subside after a few days. However, some individuals might experience restlessness or irritability.

Research shows that Biofeedback-Assisted Relaxation Training (BART) is a well-tolerated method. It treats anxiety, chronic pain, and headaches by focusing on relaxation techniques like deep breathing and muscle relaxation, which generally don't cause side effects.

Cognitive Behavioral Therapy (CBT) is another treatment under study. Research has shown it effectively reduces the frequency and severity of migraines, with few side effects reported. CBT employs techniques like distraction and problem-solving to manage pain, which are safe and well-accepted.

Cognitive Reappraisal Training (CR), similar to CBT, also uses mental strategies to manage pain. It appears safe based on its use in other conditions, though specific data on side effects for migraines is limited.

Overall, these treatments are generally well-tolerated. Amitriptyline may have some mild side effects that often lessen over time. Non-drug approaches like BART, CBT, and CR are considered safe, focusing on relaxation and mental strategies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these migraine treatments because they explore new mind and body approaches that aren't typical in standard care, which usually includes medications like triptans and beta-blockers. Cognitive Behavioral Therapy (CBT) and Cognitive Reappraisal Training (CR) focus on changing thought patterns and behaviors to manage pain, offering a psychological angle. Biofeedback-Assisted Relaxation Training (BART) uses techniques like deep breathing and guided imagery to help patients gain control over their physiological responses to pain. These approaches aim to empower patients with skills to manage their migraines, potentially leading to fewer side effects compared to traditional medication.

What evidence suggests that this trial's treatments could be effective for migraine?

Research has shown that amitriptyline, one of the treatments in this trial, can reduce the frequency of migraines. Studies have found it more effective than a placebo, which is another arm in this trial, in decreasing migraine attacks. Participants may also receive biofeedback-assisted relaxation training (BART), which a review of studies confirmed helps lower migraine frequency and severity. Cognitive Behavioral Therapy (CBT), another treatment arm, is well-supported, with evidence showing it can lessen migraine symptoms and improve related issues like anxiety and depression. Although less research exists on cognitive reappraisal training (CR), also tested in this trial, similar therapies like relaxation training have been noted to reduce migraine frequency. All these treatments offer non-drug options that might effectively manage migraines. ^{3 6 7 8 9}

Who Is on the Research Team?

Scott Powers, PhD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Robert Coghill, PhD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for young people with migraines, who have them 8-28 days a month and experience some disruption in daily life. They must be able to swallow pills, not take certain painkillers too often, and can't start new migraine prevention meds during the study. Participants need to fit in an MRI scanner and not have metal implants or severe claustrophobia.

Inclusion Criteria

I have been diagnosed with migraine, following the ICHD-3b criteria.

My daily activities are mildly to severely disrupted due to my condition.

I have had between 8 and 28 headaches in the last 28 days.

Exclusion Criteria

You weigh less than 30 kg or more than 120 kg, or your size is not suitable for an MRI scanner.

I agree to limit my use of NSAIDs to less than 3 times a week and migraine medications to less than 6 times a month.

I am not currently taking and agree not to start any migraine prevention medication during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of five treatments (CBT, BART, CR, amitriptyline, or placebo) over an 8-week period

8 weeks

Baseline and post-treatment assessments

Follow-up

Participants are monitored for changes in neural mechanisms and pain modulation after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Amitriptyline
• Biofeedback-Assisted Relaxation Training (BART)
• Cognitive Behavioral Therapy (CBT)
• Cognitive Reappraisal Training (CR)
• Placebo

Trial Overview The trial tests how well different treatments help youth with migraines by looking at brain scans, headache diaries, pain response tests, and questionnaires before/after treatment. Treatments include cognitive therapy (CBT), biofeedback training (BART), cognitive reappraisal (CR) training, amitriptyline (a medication), or placebo over 8 weeks.

How Is the Trial Designed?

Group I: Cognitive Behavioral Therapy (CBT) Experimental Treatment 1 Intervention

Cognitive Behavioral Therapy (CBT) is a mind and body based intervention using education on gate control theory of pain, behavioral strategies such as muscle relaxation and activity pacing, and cognitive strategies including distraction, problem solving, and using calming self-statements.

Group II: Amitriptyline Active Control 1 Intervention

Amitriptyline will be administered once a day at home, to be taken by mouth. Dosage will be weight-based.

Group III: Biofeedback-Assisted Relaxation Training (BART) Active Control 1 Intervention

Biofeedback-Assisted Relaxation Training (BART) is a mind and body based intervention that focuses specifically on mind and body techniques such as deep breathing, muscle relaxation, and guided imagery skills to manage pain.

Group IV: Cognitive Retraining (CR) Active Control 1 Intervention

Cognitive Retraining (CR) is a mind and body based intervention that focuses on the use of tests of evidence and other cognitive strategies such as positive coping statements and pleasant activities and mindfulness to manage pain.

Group V: Placebo Placebo Group 1 Intervention

The placebo pill will be administered once a day at home, to be taken by mouth.

Amitriptyline is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Elavil for:

• Depression
• Anxiety and Stress
• Chronic Pain
• Fibromyalgia
• Headache
• Migraine Prevention
• Neuropathic Pain

Approved in European Union as Amitriptyline for:

• Depression
• Anxiety disorders
• Chronic pain
• Fibromyalgia
• Headache
• Migraine prevention
• Neuropathic pain

Approved in Canada as Elavil for:

• Depression
• Anxiety and stress
• Chronic pain
• Fibromyalgia
• Headache
• Migraine prevention
• Neuropathic pain

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Published Research Related to This Trial

In a study of 10 female patients with episodic common migraine, 16 sessions of electromyographic biofeedback combined with relaxation training led to a significant reduction in migraine episodes, with effects lasting up to 12 months after treatment.

The study found no direct correlation between electromyographic activity and pain levels, suggesting that factors like breathing control and muscle activity may play a key role in reducing migraine pain rather than just muscle tension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Italian experience of electromyographic-biofeedback treatment of episodic common migraine: preliminary results. Grazzi, L., Bussone, G.[2019]

Nonpharmacological treatments, such as relaxation techniques, endurance sports, biofeedback, and cognitive behavioral therapy, can effectively reduce the frequency of migraine attacks.

Consulting with a healthcare provider and combining these behavioral approaches with pharmacological treatments can enhance overall treatment effectiveness for migraine management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Relaxation techniques and behavioural therapy for the treatment of migraine : Guidelines from the German Migraine and Headache Society]. Kropp, P., Meyer, B., Dresler, T., et al.[2019]

A study involving 76 patients with vascular headaches showed that a treatment program combining relaxation training and thermal biofeedback significantly reduced headache activity and medication use compared to a control group that only monitored headaches.

Both treatment groups, which received either minimal therapist contact or additional cognitive stress coping techniques, experienced similar benefits, indicating that the combination of relaxation and biofeedback is effective for managing headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled evaluation of the addition of cognitive therapy to a home-based biofeedback and relaxation treatment of vascular headache. Blanchard, EB., Appelbaum, KA., Nicholson, NL., et al.[2019]

Biofeedback-assisted relaxation training (BART) was effectively used in 61% of sessions with pediatric patients at Boston Children's Hospital, showing significant improvements in pain and mood ratings after treatment.

Patients experiencing both pain and anxiety benefited the most from BART, indicating its potential as a versatile treatment for various pediatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ready, set, relax: biofeedback-assisted relaxation training (BART) in a pediatric psychiatry consultation service. McKenna, K., Gallagher, KA., Forbes, PW., et al.[2016]

Cognitive-behavioral therapy (CBT) was highly effective in reducing headache frequency, with an average reduction of 68% after 8 sessions, compared to 56% for biofeedback and only 20% for the control group.

Improvements from CBT continued to be observed at a 12-month follow-up, and the effectiveness of CBT was linked to participants' coping skills and social support, suggesting these factors may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive-behavioral therapy versus temporal pulse amplitude biofeedback training for recurrent headache. Martin, PR., Forsyth, MR., Reece, J.[2018]

In a study of 41 patients with recurrent tension headaches, both cognitive-behavioral therapy (CBT) and amitriptyline showed significant improvements in headache activity, with CBT resulting in a 56% reduction in headache index compared to 27% for amitriptyline.

Cognitive-behavioral therapy was associated with more positive outcomes in certain areas, such as headache control and somatic complaints, although neither treatment completely eliminated headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of pharmacological (amitriptyline HCL) and nonpharmacological (cognitive-behavioral) therapies for chronic tension headaches. Holroyd, KA., Nash, JM., Pingel, JD., et al.[2019]

In a study comparing relaxation training and amitriptyline for treating young patients with tension-type headaches, both treatments showed significant clinical improvement after 3 months, indicating their efficacy.

Relaxation therapy was found to be more accepted by patients than the medication, suggesting a preference for non-pharmacological approaches, although the study's preliminary nature and small sample size mean these conclusions should be viewed cautiously.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological behavioural treatment for children and adolescents with tension-type headache: preliminary data. Grazzi, L., Andrasik, F., Usai, S., et al.[2008]

In a follow-up study of 19 out of 21 migraine patients treated with either pharmacological (ergotamine) or nonpharmacological (relaxation and biofeedback) methods, both groups maintained a significant reduction in headache activity three years later.

Patients who received nonpharmacological treatment were less likely to require additional medical treatments compared to those treated with ergotamine, suggesting that nonpharmacological methods may lead to more sustainable long-term relief from migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term maintenance of improvements achieved with (abortive) pharmacological and nonpharmacological treatments for migraine: preliminary findings. Holroyd, KA., Holm, JF., Penzien, DB., et al.[2019]

In a study of 23 patients with migraine headaches, those who received biofeedback-assisted relaxation therapy experienced greater reductions in pain and medication use compared to those who relaxed on their own.

The biofeedback group also showed significant decreases in cerebral blood flow velocity in the middle cerebral artery, indicating a potential mechanism for how this therapy alleviates migraine symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of biofeedback-assisted relaxation on migraine headache and changes in cerebral blood flow velocity in the middle cerebral artery. McGrady, A., Wauquier, A., McNeil, A., et al.[2019]

In a study of 60 adults with migraines, those who underwent 8 weeks of mindfulness-based cognitive therapy for migraine (MBCT-M) showed a significant reduction in pain catastrophizing compared to a waitlist group, indicating the therapy's efficacy in addressing negative pain perceptions.

While pain catastrophizing decreased significantly, cognitive fusion did not show a notable change, suggesting that the reduction in pain-related distress may be a key mechanism through which MBCT-M improves migraine-related disability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in cognitive appraisal in a randomized controlled trial of mindfulness-based cognitive therapy for patients with migraine. Kruse, JA., Seng, EK.[2023]

Citations

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Comparison of the efficacy of propranolol versus amitriptyline ... The average number of migraine attacks reduced in the amitriptyline and propranolol groups as the treatment duration increased. Amitriptyline is ...

2. thejournalofheadacheandpain.biomedcentral.com thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-023-01573-6

amitriptyline | The Journal of Headache and Pain So far, three placebo-controlled trials found amitriptyline significantly better than placebo at reducing a headache index or frequency, but ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21070231/

Amitriptyline in the prophylactic treatment of migraine and ... There were no significant differences in headache severity or duration between amitriptyline and placebo groups at anytime during the study.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0303846722000324

Venlafaxine can reduce the migraine attacks as well ... Both amitriptyline and venlafaxine significantly reduced the number of attacks per month (AMT: from 10.98 to 2.98, VLF: from 9.98 to 3.18), and six-item ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1610384

Trial of Amitriptyline, Topiramate, and Placebo for Pediatric ... The primary outcome was a relative reduction of 50% or more in the number of headache days in the comparison of the 28-day baseline period with ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/amitriptyline-oral-route/description/drg-20072061

Amitriptyline (oral route) - Side effects & dosage Amitriptyline may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have ...

7. nhs.uk nhs.uk/medicines/amitriptyline-for-pain/side-effects-of-amitriptyline-for-pain-and-migraine/

Side effects of amitriptyline for pain and migraine Doses of amitriptyline for pain are lower than the doses for depression. This means the common side effects tend to be milder and go away within a few days.

8. webmd.com webmd.com/drugs/2/drug-8611/amitriptyline-oral/details

Amitriptyline (Amitid, Elavil, Endep) - Uses, Side Effects, ... What are the serious side effects of amitriptyline? ; Loss of vision; Eye pain or redness; Severe headache or vomiting ; Very increased energy ...

9. drugs.com drugs.com/amitriptyline.html

Amitriptyline Uses, Dosage, Side Effects, Warnings Amitriptyline can cause other serious side effects. Call your doctor at once if you have: signs of a blood clot - sudden numbness or weakness, ...