Migraine
Conditions
Keywords
Naltrexone, Acetaminophen, Acute migraine, Low-dose naltrexone, Anxiety
Brief 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. 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.
Detailed description
This study evaluating naltrexone-acetaminophen in the acute treatment of migraine.
Interventions
DRUGStage 1: Naltrexone/Acetaminophen
Combination
DRUGStage 1: Naltrexone
Naltrexone alone
DRUGStage 1: Acetaminophen
Acetaminophen alone
DRUGStage1: Placebo
Matching placebo
DRUGStage 2: Naltrxone/Acetaminophen high dose
Combination high dose
DRUGStage 2: Naltrexone/Acetaminophen medium dose
Combination medium dose
DRUGStage 2: Naltrxone/Acetaminophen low dose
Combination low dose
DRUGStage 2: Placebo
Matching Placebo
Sponsors
Allodynic Therapeutics, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, Double-Blind, Placebo-Controlled, Parallel-Group
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Ages 18 to 75 years, inclusive. 2. 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). 3. Migraine onset before age 50 years. 4. Read, write, and speak English 5. BMI Higher than 20 and Lower than 34 6. 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.
Exclusion criteria
1. Pregnant or nursing women or those planning a pregnancy. 2. Used opioids (including methadone and buprenorphine), barbiturate-containing medications, muscle relaxants, or benzodiazepines within 3 months prior to screening. 3. Used any recreational drugs in the past 3 months. 4. 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. 5. Uncontrolled cardiovascular or cerebrovascular disease or a history of heart failure, atrial fibrillation, or myocardial infarction. 6. Uncontrolled hypertension (systolic/diastolic blood pressure ˃ 140/90 mmHg) or diabetes. 7. Immediate family members or same household members participating in the study. 8. Site personnel, their friends, and family. 9. Abnormal laboratory or ECG results. 1. Aspartate transaminase (AST/SGOT), alanine transaminase (ALT/SGPT), or alkaline Phosphatase ≥ 1.5 x Upper Limit of Normal (ULN). creatinine ≥ 1.5 x ULN. 2. BBB or intraventricular conduction defect with a QRS duration ≥ 150 msec. ST-T wave abnormalities. 3. Hemoglobin \< 10 g/dL 4. Neutrophil count ≤ 1000/μL 5. Cholesterol ≥ 300 mg/dL 6. Triglycerides ≥ 500 mg/dL Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects with acute migraine who achieved freedom from pain after dosing | 2 hours 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. |
| Proportion of subjects with acute migraine who achieved freedom from migraine's Most Bothersome Symptoms (MBS) after dosing | 2 hours 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects with acute migraine who achieved sustained pain relief from 2 to 24 hours | 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. |
| Functional disability at 2 hours | 2 hours after dosing | 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. |
| Functional disability at 24 hours | 24 hours after dosing | 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. |
| Use of rescue medications within 24 hours | within 24 hours | Rescue medication use refers to the use of an additional medication to treat the current migraine. |
| Pain relapse within 48 hours | 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. |
| Proportion of subjects with acute migraine who achieved pain relief | 2 hours after dosing | Pain relief is defined as a reduction in headache pain severity from moderate or severe to mild or no headache pain. |
| Proportion of subjects with acute migraine who achieved freedom from photophobia | 2 hours after dosing | Freedom from photophobia is defined as absence of photophobia |
| Proportion of subjects with acute migraine who achieved freedom from phonophobia | 2 hours after dosing | Freedom from phonophobia is defined as absence of phonophobia |
| Proportion of subjects with acute migraine who achieved freedom from nausea | 2 hours after dosing | Freedom from nausea is defined as absence of nausea |
| The proportion of subjects with acute migraine who achieved sustained pain freedom from 2 to 24 hours | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Self-reported tense feelings score | 2 hours after dosing | Self-reported tense feelings on a 4-point scale: (0=Not at all, 1=Slightly, 2=Moderate, 3=Extremely). |
| Self-reported hurt feelings score | 2 hours after dosing | Self-reported hurt feelings on a 4-point scale: (0=Not at all, 1=Slightly, 2=Moderate, 3=Extremely). |
| Hamilton Anxiety Rating Scale score | Baseline (Randomization Visit) to 2 hours after dosing | The Hamilton Anxiety Rating Scale is a validated assessment tool for measuring anxiety symptoms. The scale consists of fourteen items designed to assess the severity of anxiety on a scale of zero to four, with four being the most severe. |
| Self-reported overall sense of wellbeing | 2 hours after dosing | Self-reported overall sense of wellbeing (physical and emotional) is a subjective measurement that reflects an individual's perception of their physical and emotional health. It is typically assessed on a 4-point scale, ranging from 0 (Poor) to 3 (Superb), with 1 (Okay) and 2 (Good) representing intermediate levels of wellbeing. This measurement considers factors such as physical pain, positive emotions, life satisfaction, stress management, and the absence of negative emotions like depression and anxiety. |
Countries
United States
Outcome results
None listed