Migraine > Naltrexone-Acetaminophen Combination

Naltrexone/Acetaminophen for Migraine Headaches

(AT-06 Trial)

Recruiting in Palo Alto (17 mi)

Overseen By Natalia Belikova, MD PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Annette C. Toledano MD

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

Disqualifiers: Pregnancy, Uncontrolled hypertension, Diabetes, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

* This two-stage clinical trial will assess a novel combination therapy for acute migraine. In Stage 1 (factorial), participants will receive the combination, each individual component, or placebo. In Stage 2 (dose-finding), they will test three doses of the combination. Before both stages, participants will complete a run-in period, documenting a migraine attack without study medication. They will then treat one migraine attack in each stage. * 4 visits * Requirements: * Migraine Diagnosis * BMI below 34 * Read, write, and speak English * No opioids, marijuana, benzodiazepines, or excessive alcohol.

Will I have to stop taking my current medications?

The trial requires that you do not use opioids, marijuana, benzodiazepines, or excessive alcohol. If you use medications to treat headaches or other pain more than 10 days a month, you may not be eligible. The protocol does not specify other medication restrictions, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Naltrexone-Acetaminophen Combination for treating migraine headaches?

Research shows that acetaminophen, a component of the combination, is effective in treating migraine headaches. Studies have demonstrated that acetaminophen alone or in combination with other drugs can help alleviate migraine pain.

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How does the Naltrexone-Acetaminophen drug differ from other migraine drugs?

The Naltrexone-Acetaminophen combination is unique because it combines naltrexone, which is typically used to treat addiction, with acetaminophen, a common pain reliever, offering a novel approach to migraine treatment that differs from standard options like triptans or NSAIDs (non-steroidal anti-inflammatory drugs).

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Eligibility Criteria

This trial is for adults aged 18-75 with a history of migraines, diagnosed before age 50. Participants must have experienced migraines lasting 4-72 hours and occurring 2-8 times per month over the last year. They should not be using opioids, marijuana, benzodiazepines, or excessive alcohol and must have a BMI below 34. Those on stable migraine prevention medication can join if they maintain their dosage.

Inclusion Criteria

My BMI is 36 or less.

I can avoid opioids for the duration of the study and 7 days after.

I am between 18 and 75 years old.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Participants complete a run-in period, documenting a migraine attack without study medication

1 week

1 visit (in-person)

Stage 1 Treatment

Participants receive one dose of either the combination therapy, each individual component, or placebo for a qualifying migraine attack

1 week

1 visit (in-person)

Stage 2 Treatment

Participants test three doses of the combination therapy for a qualifying migraine attack

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The study tests a new combination therapy for acute migraine in two stages: Stage 1 compares Naltrexone/Acetaminophen combo to each component alone and placebo; Stage 2 finds the best dose of the combo. Participants will treat one attack per stage after documenting an untreated attack.

Group I: Stage 2: Naltrexone/Acetaminophen-medium dose Experimental Treatment 1 Intervention

One dose for a qualifying migraine attack

Group II: Stage 2: Naltrexone/Acetaminophen-low dose Experimental Treatment 1 Intervention

One dose for a qualifying migraine attack

Group III: Stage 2: Naltrexone/Acetaminophen-high dose Experimental Treatment 1 Intervention

One dose for a qualifying migraine attack

Group IV: Stage 1: Naltrexone/Acetaminophen Experimental Treatment 1 Intervention

One dose for a Qualifying Migraine Attack

Group V: Stage 1: Naltrexone Active Control 1 Intervention

One dose for a Qualifying Migraine Attack

Group VI: Satge 1: Acetaminophen Active Control 1 Intervention

One dose for a Qualifying Migraine Attack

Group VII: Stage 1: Placebo Placebo Group 1 Intervention

One dose for a Qualifying Migraine Attack

Group VIII: Stage 2: Placebo Placebo Group 1 Intervention

One dose for a qualifying migraine attack

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Keystone Clinical Research North Miami, FL

Who Is Running the Clinical Trial?

Annette C. Toledano MD Lead Sponsor

Allodynic Therapeutics, LLC Lead Sponsor

Allodynic Therapeutics, Inc Lead Sponsor

References

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

Efficacy and tolerability of coadministration of rizatriptan and acetaminophen vs rizatriptan or acetaminophen alone for acute migraine treatment. [2019] To evaluate the efficacy and tolerability of coadministration of rizatriptan and acetaminophen in the acute treatment of migraine.

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

A randomized, placebo-controlled trial of acetaminophen for treatment of migraine headache. [2022] To evaluate the efficacy and safety of acetaminophen 1000 mg for the treatment of episodic migraine headache.

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

Comparison of paracetamol (apotel®) and morphine in reducing post pure head trauma headache. [2021] This randomized, clinical trial evaluates the analgesic and safety of paracetamol and Morphine in management of headache.

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

Efficacy and safety of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain: three double-blind, randomized, placebo-controlled trials. [2019] To assess the effectiveness of the nonprescription combination of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain.

5. New Zealand pubmed.ncbi.nlm.nih.gov

Acute treatment of migraines. [2021] Migraine is a prevalent and disabling brain disorder that costs billions of dollars annually in direct healthcare costs, and school and work absenteeism and presenteeism. The objective of acute treatment is a cost-effective, rapid restoration of functional ability, with minimal recurrence and adverse effects. The acute treatment of migraine includes specific drugs, which currently all have vasoconstrictive effects (dihydroergotamine and triptans), and nonspecific drugs that include paracetamol (acetaminophen), combination analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), dopamine antagonists, narcotics and corticosteroids. NSAIDs have both peripheral and central effects on reversing migraine, and so may represent the best alternative for patients who cannot use triptans and ergots due to vascular contraindications. Narcotics and habituating medications should be avoided in the acute treatment of migraine, as the risk for transformation to chronic daily headache is excessively high at a relatively infrequent rate of exposure.

6. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Medical Treatment Guidelines for Acute Migraine Attacks. [2018] In 2015, the American Headache Society (AHS) amended the treatment guideline of acute migraine based on evidence-based medicine (EBM) that all triptans in any form of preparations, acetaminophen, and non-steroid anti-inflammation drugs-NSAID (aspirin, diclofenac, ibuprofen, naproxen), sumatriptan/naproxen, combined acetaminophen/aspirin/caffeine are considered effective (Level A). Previously effective drugs as prochlorperazine, and dihydroergotamine-DHE (excluded inhaled form) were downrated to probable effective (Level B). Taiwan Headache Society published its treatment guideline for acute migraine attack in 2007. It should be updated based on the new available evidence. The Treatment Guideline Subcommittee of Taiwan Headache Society reviewed the recent trials, evaluated the grade of evidence, and appraised the clinical efficacy to reach a new consensus. We also referred to the guidelines from United States, Europe, Canada and other countries to make this one meets our needs and feasible. Acute medications currently available in Taiwan can be categorized into "migraine-specific"and"migraine-nonspecific" groups. Migraine-specific triptans and migraine-nonspecific nonsteroidal antiinflammatory drugs (NSAIDs) have the best levels of evidence, and are recommended as the first-line medications for acute migraine attacks. The administration should follow the concept of "stratified care". For mild to moderate migraine attacks, oral NSAIDs are the first choice; with oral aspirin, combination analgesics, intravenous/intramuscular NSAIDs as alternatives. For moderate to severe attacks, oral or nasal spray triptans and ergotamine/caffeine compounds are recommended and should be administered in the early stage of migraine attacks. Antiemetics can be used as supplement to alleviate nausea and vomiting. Notably, a combination of a triptan and a NSAID yielded a better efficacy compared with either therapy alone. Parenteral steroid and fluid supply are the first choice in treatment of status migrainosus. Acetaminophen is suitable for mild to moderate migraine attacks and remains the first choice for children and pregnant women. Opiates are not recommended for acute migraine treatment at the present time because of serious adverse events. To prevent medication-overuse headache, the use of acute treatment should be limited to a maximum of ten days a month.

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

The efficacy and tolerability of a fixed combination of acetylsalicylic acid, paracetamol, and caffeine in patients with severe headache: a post-hoc subgroup analysis from a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study. [2013] We investigated efficacy and tolerability of two tablets of the fixed combination of 250 mg acetylsalicylic acid (ASA) + 200 mg paracetamol + 50 mg caffeine (Thomapyrin) in comparison to two tablets of placebo in a post-hoc analysis of a subgroup of patients with severe headache.

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

Results of a multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study comparing the fixed combination of acetaminophen, acetylsalicylic acid, and caffeine with ibuprofen for acute treatment of patients with severe migraine. [2014] In a multicenter, double-blind, randomized, parallel-group, placebo-controlled, single-dose study (n = 1555), a fixed combination of acetaminophen 500 mg, acetylsalicylic acid 500 mg, and caffeine 130 mg (AAC) was compared with ibuprofen 400 mg (IB) and placebo (PLA) for acute treatment of migraine.