Low-Dose Naltrexone and Acetaminophen Combination and Its Components in the Acute Treatment of Migraine

Migraine With or Without Aura Clinical Trial

— ANODYNE-1  

Official title:

A Clinical Trial to Assess a Single Dose of Low-Dose Naltrexone and Acetaminophen Combination and Its Components in the Acute Treatment of Migraine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03061734
• Other study ID #: ANODYNE-1
• Status: Completed
• Phase: Phase 2
• Start date: February 18, 2017
• Est. completion date: February 8, 2018

Study information

• Verified date: April 2021
• Source: Allodynic Therapeutics, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study consists of a screening visit, out-patient treatment of a moderate or severe migraine attack with a single dose of the study medication within 8 weeks, and End-of-Study Visit 2-7 days after dosing.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: February 8, 2018
• Est. primary completion date: February 8, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female 18 years of age or older.

2. History of migraine with or without aura according to the International Classification of Headache Disorders (ICHD)-3rd edition (beta version) for at least one-year with first migraine prior to age 50.

3. Migraine-associated nausea with =half of migraine attacks.

4. 2 - 8 migraines per month in each of the previous 3 months.

5. The patient is able to complete study questionnaires, comply with the study requirements and restrictions, and willing to provide written informed consent and authorize HIPAA.

6. The female patient who is premenopausal or postmenopausal less than 1 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 adequate and reliable contraception throughout the study (e.g., barrier with additional spermicidal, intra-uterine device, hormonal contraception). The male patient must be surgically sterile or commit to the use of 2 different methods of birth control during the study and for 28 days after taking the study drug.

Exclusion Criteria:

1. The patient in the opinion of the investigator, may have medication-overuse headache pain (as defined by ICHD - 3 beta criteria for medication-overuse headache), (analgesic, opioid, ergotamine or triptan overuse) during the 3 months preceding screening.

2. The patient in the opinion of the investigator has chronic migraine (as defined by ICHD - 3 beta criteria for chronic migraine).

3. History of cluster headache or neurologically complicated migraine (hemiplegic, basilar, retinal, ophthalmoplegic migraine).

4. Initiation or change in medications with possible migraine prophylactic effects during 3 months before inclusion into the trial (E.g., calcium channel blockers, tricyclic antidepressants, beta-blockers, selective serotonin re-uptake inhibitors (SSRIs), serotonin-norepinephrine re-uptake inhibitors (SNRIs), or Botox).

5. Any concurrent medical or psychiatric condition, this includes, but is not limited to chronic unstable debilitating diseases, significant renal or hepatic impairment.

6. A history within the previous 3 years of abuse of any drug, prescription, illicit, or alcohol.

7. The Female patient is pregnant or breast-feeding. The Male patient is not practicing 2 different methods of birth control with their partner during the study, and for 28 days after the investigational drug last dose or will not remain abstinent during the study, and for 28 days after the last dose.

8. Use of opiates or barbiturates more than 3 days per month.

9. Known-hypersensitivity reaction to any of the components of the investigational drug.

10. Consumption of analgesic medication for other conditions on a regular basis, (nonsteroidal anti-inflammatory drugs, or acetaminophen, or muscle relaxants).

11. Use of emergency care treatment more than 3 times in the previous 6 months.

12. Participation in another study with an investigational drug within 30 days prior to randomization and/or a plan to participate during the study.

Related Conditions & MeSH terms

• Migraine Disorders
• Migraine With or Without Aura

Intervention

Drug:
• Naltrexone and Acetaminophen
Naltrexone plus acetaminophen
• Naltrexone and Acetaminophen-High Dose
Naltrexon (high dose) plus acetaminophen
• Naltrexone Alone (regular dose)
Naltrexone Alone plus Placebo
• Acetaminophen Alone
Acetaminophen Alone plus Placebo
• Matching Placebo
Two Placebo capsules

Locations

Country	Name	City	State
United States	Annette C. Toledano MD	North Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Allodynic Therapeutics, LLC

Country where clinical trial is conducted

United States, 

References & Publications (11)

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: 10.1177/095679761 — View Citation

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). E — View Citation

Kaki AM, El-Yaski AZ, Youseif E. Identifying neuropathic pain among patients with chronic low-back pain: use of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale. Reg Anesth Pain Med. 2005 Sep-Oct;30(5):422-8. — View Citation

Kato J, Svensson CI. Role of extracellular damage-associated molecular pattern molecules (DAMPs) as mediators of persistent pain. Prog Mol Biol Transl Sci. 2015;131:251-79. doi: 10.1016/bs.pmbts.2014.11.014. Epub 2015 Jan 30. Review. — View Citation

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- — View Citation

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. — View Citation

Su M, Ran Y, He Z, Zhang M, Hu G, Tang W, Zhao D, Yu S. Inhibition of toll-like receptor 4 alleviates hyperalgesia induced by acute dural inflammation in experimental migraine. Mol Pain. 2018 Jan-Dec;14:1744806918754612. doi: 10.1177/1744806918754612. Epu — View Citation

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: 10.111 — View Citation

Watkins LR, Hutchinson MR, Ledeboer A, Wieseler-Frank J, Milligan ED, Maier SF. Norman Cousins Lecture. Glia as the "bad guys": implications for improving clinical pain control and the clinical utility of opioids. Brain Behav Immun. 2007 Feb;21(2):131-46. — View Citation

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 — View Citation

Younger J, Mackey S. Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study. Pain Med. 2009 May-Jun;10(4):663-72. doi: 10.1111/j.1526-4637.2009.00613.x. Epub 2009 Apr 22. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	% of patients who experienced adverse events	treatment related Adverse Events	48 hours
Primary	% of patients reporting no headache pain.	Self-reported headache pain on a four-point Likert scale.	2 hours post-dose
Primary	% of patients having absence of most bothersome migraine-associated symptom (MBS).	MBS was prospectively identified at baseline. Self-reported MBS as present or absent.	2 hours post-dose
Primary	% of patients who have "sustained pain freedom"	Defined as having no headache pain at 2 hours after dose, with no use of rescue medication and no relapse of headache pain within 24 hours after administration of the investigational drug.	24-hour post-dose.
Secondary	% of patients having absence of nausea, photophobia, phonophobia, and neck/shoulder pain	Self-reported the current status of their associated symptom as present or absent.	24-hour post-dose.
Secondary	% of patients who used rescue medications		2-24 hours
Secondary	% of patients who had headache pain relapse.	Defined as the return of headache of any severity within 48 hours after administration of the investigational drug, when the patient was pain-free at 2 hours after the administration of the investigational drug.	2-48 hours

External Links

•   2009-2013 Pain Research Advances | Interagency Pain ...Thus, identifying potential new medications is critical. Recent evidence indicates a pivotal role for the receptor known as toll-like receptor 4 (TLR4 ...