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MigrainePhase 2AT-06NCT05685225

Single-Site Study of Naltrexone/Acetaminophen for the Acute Treatment of Migraine: A Phase 2 Randomized Trial

A Phase 2 study testing Stage 1: Naltrexone/Acetaminophen, Stage 1: Naltrexone and Stage 1: Acetaminophen in people with Migraine, run by Allodynic Therapeutics, Inc at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Migraine
What is being tested?
Stage 1: Naltrexone/Acetaminophen, Stage 1: Naltrexone and Stage 1: Acetaminophen
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteUnited States
Study dates
31 Jan 2025to 2 Dec 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ages 18 to 75 years, inclusive.
  • At least 1-year of history of migraine with or without aura as defined by the International Classification of Headache Disorders 3rd edition 17 (ICHD-3).
  • Migraine onset before age 50 years.
  • Read, write, and speak English
  • BMI Higher than 20 and Lower than 34
  • The female subject who is premenopausal or postmenopausal less than one year or have not had surgical sterilization (i.e., tubal ligation, partial or complete hysterectomy) must have a negative urine pregnancy test, be non-lactating, and commit to using two methods of adequate and reliable contraception throughout the study and for 28 days after taking the last dose of the study medication (e.g., barrier with an additional spermicidal, intra- uterine device, hormonal contraception). Male subjects must be surgically sterile (the procedure occurred greater than 6 months before the Screening Visit) or commit to using two different birth control methods during the study and for 28 days after the last dose of the study medication.

Who cannot join

  • Pregnant or nursing women or those planning a pregnancy.
  • Used opioids (including methadone and buprenorphine), barbiturate-containing medications, muscle relaxants, or benzodiazepines within 3 months prior to screening.
  • Used any recreational drugs in the past 3 months.
  • Use of medications to treat headaches more than 10 days per month in the past 3 months or use of any pain medication for other pain syndromes for more than 10 days per month.
  • Uncontrolled cardiovascular or cerebrovascular disease or a history of heart failure, atrial fibrillation, or myocardial infarction.
  • Uncontrolled hypertension (systolic/diastolic blood pressure ˃ 140/90 mmHg) or diabetes.
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  • Immediate family members or same household members participating in the study.
  • Site personnel, their friends, and family.
  • Abnormal laboratory or ECG results.
  • Aspartate transaminase (AST/SGOT), alanine transaminase (ALT/SGPT), or alkaline Phosphatase ≥ 1.5 x Upper Limit of Normal (ULN). creatinine ≥ 1.5 x ULN.
  • BBB or intraventricular conduction defect with a QRS duration ≥ 150 msec. ST-T wave abnormalities.
  • Hemoglobin < 10 g/dL
  • Neutrophil count ≤ 1000/μL
  • Cholesterol ≥ 300 mg/dL
  • Triglycerides ≥ 500 mg/dL Additional exclusion criteria may apply.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Keystone Clinical Research

    North Miami, Florida, 33181

Other trials in United States

About this study

Official title: Safety and Efficacy of Naltrexone/Acetaminophen for the Acute Treatment of Migraine: A Single-Site, Phase 2 Randomized 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.
Read the detailed description

This study evaluating naltrexone-acetaminophen in the acute treatment of migraine.

Conditions
Migraine
Being tested
Stage 1: Naltrexone/Acetaminophen, Stage 1: Naltrexone, Stage 1: Acetaminophen, Stage1: Placebo, Stage 2: Naltrxone/Acetaminophen high dose
Keywords
Naltrexone, Acetaminophen, Acute migraine, Low-dose naltrexone, Anxiety
Medical subject headings
Migraine Disorders, Anxiety Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Stage 1: Naltrexone/AcetaminophenDrug

    Also called ALLOD-2

    Combination

  • Stage 1: NaltrexoneDrug

    Naltrexone alone

  • Stage 1: AcetaminophenDrug

    Acetaminophen alone

  • Stage1: PlaceboDrug

    Matching placebo

  • Stage 2: Naltrxone/Acetaminophen high doseDrug

    Also called ALLOD-2

    Combination high dose

  • Stage 2: Naltrexone/Acetaminophen medium doseDrug

    Also called ALLOD-2

    Combination medium dose

  • Stage 2: Naltrxone/Acetaminophen low doseDrug

    Also called ALLOD-2

    Combination low dose

  • Stage 2: PlaceboDrug

    Matching Placebo

Study groups in NCT05685225
Study groupRoleWhat they receive
Stage 1: Naltrexone/AcetaminophenExperimentalOne dose for a Qualifying Migraine Attack
Receives: Drug: Stage 1: Naltrexone/Acetaminophen
Stage 1: NaltrexoneActive comparatorOne dose for a Qualifying Migraine Attack
Receives: Drug: Stage 1: Naltrexone
Satge 1: AcetaminophenActive comparatorOne dose for a Qualifying Migraine Attack
Receives: Drug: Stage 1: Acetaminophen
Stage 1: PlaceboPlacebo comparatorOne dose for a Qualifying Migraine Attack
Receives: Drug: Stage1: Placebo
Stage 2: Naltrexone/Acetaminophen-high doseExperimentalOne dose for a qualifying migraine attack
Receives: Drug: Stage 2: Naltrxone/Acetaminophen high dose
Stage 2: Naltrexone/Acetaminophen-medium doseExperimentalOne dose for a qualifying migraine attack
Receives: Drug: Stage 2: Naltrexone/Acetaminophen medium dose
Stage 2: Naltrexone/Acetaminophen-low doseExperimentalOne dose for a qualifying migraine attack
Receives: Drug: Stage 2: Naltrxone/Acetaminophen low dose
Stage 2: PlaceboPlacebo comparatorOne dose for a qualifying migraine attack
Receives: Drug: Stage 2: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of subjects with acute migraine who achieved freedom from pain after dosing

    Freedom from pain is defined as the absence of headache pain from moderate or severe pain at baseline, without the use of rescue medication. The pain is measured on a 4-point scale, with 0 indicating no pain, 1 for mild pain, 2 for moderate pain, and 3 for severe pain.

    Measured: 2 hours after dosing

  2. Proportion of subjects with acute migraine who achieved freedom from migraine's Most Bothersome Symptoms (MBS) after dosing

    MBS freedom is defined as the absence of the identified Most Bothersome Symptom (MBS), which can be nausea, photophobia, or phonophobia. The MBS is measured on a binary scale, either absent or present.

    Measured: 2 hours after dosing

Secondary outcomes (10)

  1. Proportion of subjects with acute migraine who achieved pain relief

    Pain relief is defined as a reduction in headache pain severity from moderate or severe to mild or no headache pain.

    Measured: 2 hours after dosing

  2. Proportion of subjects with acute migraine who achieved freedom from photophobia

    Freedom from photophobia is defined as absence of photophobia

    Measured: 2 hours after dosing

  3. Proportion of subjects with acute migraine who achieved freedom from phonophobia

    Freedom from phonophobia is defined as absence of phonophobia

    Measured: 2 hours after dosing

  4. Proportion of subjects with acute migraine who achieved freedom from nausea

    Freedom from nausea is defined as absence of nausea

    Measured: 2 hours after dosing

  5. Proportion of subjects with acute migraine who achieved sustained pain relief from 2 to 24 hours

    Sustained pain relief is defined as the reduction of headache pain severity from moderate or severe intensity to mild without the use of rescue medication.

    Measured: 2 to 24 hours

  6. The proportion of subjects with acute migraine who achieved sustained pain freedom from 2 to 24 hours

    Sustained pain freedom is defined as the absence of any headache pain of any intensity without the use of rescue medication.

    Measured: 2 to 24 hours

  7. Functional disability at 2 hours

    Functional disability refers to the inability to perform activities of daily living or work tasks to a normal level due to physical, mental, or sensory impairments. It is measured on a scale of 0 to 3, where 0 indicates normal function and 3 indicates the need for bedrest due to severe impairment.

    Measured: 2 hours after dosing

  8. Functional disability at 24 hours

    Functional disability refers to the inability to perform activities of daily living or work tasks to a normal level due to physical, mental, or sensory impairments. It is measured on a scale of 0 to 3, where 0 indicates normal function and 3 indicates the need for bedrest due to severe impairment.

    Measured: 24 hours after dosing

  9. Use of rescue medications within 24 hours

    Rescue medication use refers to the use of an additional medication to treat the current migraine.

    Measured: within 24 hours

  10. Pain relapse within 48 hours

    Pain relapse refers to the reappearance of headache pain of any severity when the subject had been free of pain 2 hours after dosing.

    Measured: within 48 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jan 2023
  2. Study start31 Jan 2025
  3. Primary completion2 Dec 2025
  4. Study completion2 Dec 2025

Why it stopped: No participants enrolled; study suspended due to recruitment challenges.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, Double-Blind, Placebo-Controlled, Parallel-Group
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05685225
Sponsor's protocol ID
AT-06
Acronym
AT-06
Status last verified
Dec 2025
First submitted
27 Dec 2022
Last updated
8 Dec 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lipton RB, Baggish JS, Stewart WF, Codispoti JR, Fu M. Efficacy and safety of acetaminophen in the treatment of migraine: results of a randomized, double-blind, placebo-controlled, population-based study. Arch Intern Med. 2000 Dec 11-25;160(22):3486-92. doi: 10.1001/archinte.160.22.3486.

    PubMed 11112243

  • Wieseler J, Ellis A, McFadden A, Stone K, Brown K, Cady S, Bastos LF, Sprunger D, Rezvani N, Johnson K, Rice KC, Maier SF, Watkins LR. Supradural inflammatory soup in awake and freely moving rats induces facial allodynia that is blocked by putative immune modulators. Brain Res. 2017 Jun 1;1664:87-94. doi: 10.1016/j.brainres.2017.03.011. Epub 2017 Mar 16.

    PubMed 28322750

  • Marmura MJ, Silberstein SD, Schwedt TJ. The acute treatment of migraine in adults: the american headache society evidence assessment of migraine pharmacotherapies. Headache. 2015 Jan;55(1):3-20. doi: 10.1111/head.12499.

    PubMed 25600718

  • Hutchinson MR, Zhang Y, Brown K, Coats BD, Shridhar M, Sholar PW, Patel SJ, Crysdale NY, Harrison JA, Maier SF, Rice KC, Watkins LR. Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4). Eur J Neurosci. 2008 Jul;28(1):20-9. doi: 10.1111/j.1460-9568.2008.06321.x.

    PubMed 18662331

  • Nicotra L, Loram LC, Watkins LR, Hutchinson MR. Toll-like receptors in chronic pain. Exp Neurol. 2012 Apr;234(2):316-29. doi: 10.1016/j.expneurol.2011.09.038. Epub 2011 Oct 6.

    PubMed 22001158

  • Ellis A, Wieseler J, Favret J, Johnson KW, Rice KC, Maier SF, Falci S, Watkins LR. Systemic administration of propentofylline, ibudilast, and (+)-naltrexone each reverses mechanical allodynia in a novel rat model of central neuropathic pain. J Pain. 2014 Apr;15(4):407-21. doi: 10.1016/j.jpain.2013.12.007. Epub 2014 Jan 9.

    PubMed 24412802

  • Lewis SS, Loram LC, Hutchinson MR, Li CM, Zhang Y, Maier SF, Huang Y, Rice KC, Watkins LR. (+)-naloxone, an opioid-inactive toll-like receptor 4 signaling inhibitor, reverses multiple models of chronic neuropathic pain in rats. J Pain. 2012 May;13(5):498-506. doi: 10.1016/j.jpain.2012.02.005. Epub 2012 Apr 20.

    PubMed 22520687

  • Wang X, Zhang Y, Peng Y, Hutchinson MR, Rice KC, Yin H, Watkins LR. Pharmacological characterization of the opioid inactive isomers (+)-naltrexone and (+)-naloxone as antagonists of toll-like receptor 4. Br J Pharmacol. 2016 Mar;173(5):856-69. doi: 10.1111/bph.13394. Epub 2016 Feb 4.

    PubMed 26603732

  • Selfridge BR, Wang X, Zhang Y, Yin H, Grace PM, Watkins LR, Jacobson AE, Rice KC. Structure-Activity Relationships of (+)-Naltrexone-Inspired Toll-like Receptor 4 (TLR4) Antagonists. J Med Chem. 2015 Jun 25;58(12):5038-52. doi: 10.1021/acs.jmedchem.5b00426. Epub 2015 Jun 5.

    PubMed 26010811

  • Roberts ID, Krajbich I, Way BM. Acetaminophen influences social and economic trust. Sci Rep. 2019 Mar 11;9(1):4060. doi: 10.1038/s41598-019-40093-9.

    PubMed 30858394

  • Dewall CN, Macdonald G, Webster GD, Masten CL, Baumeister RF, Powell C, Combs D, Schurtz DR, Stillman TF, Tice DM, Eisenberger NI. Acetaminophen reduces social pain: behavioral and neural evidence. Psychol Sci. 2010 Jul;21(7):931-7. doi: 10.1177/0956797610374741. Epub 2010 Jun 14.

    PubMed 20548058

  • Wardle MC, Bershad AK, de Wit H. Naltrexone alters the processing of social and emotional stimuli in healthy adults. Soc Neurosci. 2016 Dec;11(6):579-91. doi: 10.1080/17470919.2015.1136355. Epub 2016 Jan 22.

    PubMed 26710657

  • Devlen J. Anxiety and depression in migraine. J R Soc Med. 1994 Jun;87(6):338-41.

    PubMed 8046705

  • Buse DC, Reed ML, Fanning KM, Bostic R, Dodick DW, Schwedt TJ, Munjal S, Singh P, Lipton RB. Comorbid and co-occurring conditions in migraine and associated risk of increasing headache pain intensity and headache frequency: results of the migraine in America symptoms and treatment (MAST) study. J Headache Pain. 2020 Mar 2;21(1):23. doi: 10.1186/s10194-020-1084-y.

    PubMed 32122324

  • Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.

    PubMed 29368949

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Stage 1: Naltrexone/Acetaminophen, Stage 1: Naltrexone and Stage 1: Acetaminophen in people with Migraine, run by Allodynic Therapeutics, Inc at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 8 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of subjects with acute migraine who achieved freedom from pain after dosing (time frame: 2 hours after dosing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05685225, which also lists 43 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2025.

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