Endometriosis
Conditions
Keywords
endometriosis, chronic pain, intravenous lidocaine
Brief summary
We are doing this research study to find out if intravenous (in your vein, IV) lidocaine can lessen pain from endometriosis. The U.S. Food and Drug Administration (FDA) has approved intravenous lidocaine to treat irregular heart beats, but the FDA has not approved intravenous lidocaine to treat pain from endometriosis. Intravenous lidocaine has been used for more than 25 years to treat different acute and chronic pain conditions but has not yet been studied for endometriosis pain. This is a cross-over trial over two months where one month you will receive the active medication (lidocaine) and one month you will receive the active placebo (diphenhydramine, commonly known as benadryl). We will compare the effect on pain from endometriosis of lidocaine to active placebo.
Interventions
DRUGIV Lidocaine
DRUGIV diphenhydramine
Sponsors
Pfizer
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Reproductive age women ages 18 - 50 * Endometriosis diagnosed laparoscopically or by primary care physician or gynecologist using clinical criteria * Pain for \> 6 months * Pain most intense around time of menstrual cycle. Pain at least 5 on a 0-10 scale. * Receiving regular monthly menses (cannot be receiving Depo-provera injections)
Exclusion criteria
* Pregnant or breastfeeding * On lupron therapy * History of myocardial infarction or cardiac arrhythmias including Wolff-Parkinson-White, severe sinoatrial, atrioventricular or intraventricular heart block in the absence of a pacemaker * History of seizure disorder * Significant anxiety, psychosis or other cognitive disorder limiting completion of study procedures * History of alcohol or substance abuse * Chronic pain symptoms other than chronic pelvic pain (excluding migraine pain) * Known hypersensitivity to amide type anesthetics * Known hypersensitivity to diphenhydramine (benadryl) * History of treatment with lidocaine or mexiletene * Having or showing signs and symptoms of liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Visual Analogue Scale (VAS) | 15 minutes after start of infusion, 30 minutes after start of infusion, and 30 minutes after infusion complete from BL (pre-infusion) | Visual Analogue Scale (VAS) ranges from 0 (no pain) to 10 (the worse imaginable pain). Change scores are calculated from baseline (pre-infusion) at 15 minutes after start of infusion, 30 minutes after start of infusion, and 30 minutes after infusion complete: (15 minutes after start of infusion value - BL pre-infusion value) (30 minutes after start of infusion value - BL pre-infusion value) (30 minutes after infusion complete value - BL pre-infusion value) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Short Form McGill Pain Questionnaire 2 | 30 minutes, 1 week, and 1 month post-treatment from BL (pre-infusion) | Short-form McGill Pain Questionnaire version 2 consists of 22 pain items (Throbbing, Shooting, Stabbing, Sharp, Cramping, Gnawing, Hot-burning, Aching, Heavy, Tender, Splitting, Tiring-exhausting, Sickening, Fearful, Punishing-cruel, Electric-shock, Cold-freezing, Piercing, Pain caused by light touch, Itching, Tingling or 'pins and needles', and Numbness). Each item is rated on a scale from 0-10, where 0=none, and 10=worst possible pain. The total pain score is the sum of these 22 items, ranging from 0-220. Change scores are calculated from baseline (pre-infusion) at 30 minutes, 1 week, and 1 month post-treatment: (30 minutes post-treatment value - BL pre-infusion value) (1 week post-treatment value - BL pre-infusion value) (1 month post-treatment value - BL pre-infusion value) |
| Change in Brief Pain Inventory (BPI): Pain on Average | 1 day, 1 week, and 1 month post-treatment from BL (pre-infusion) | The Pain on Average score in the Brief Pain Inventory is rated from 0-10, where 0 is no pain, and 10 is pain as bad as you can imagine. Change scores are calculated from baseline (pre-infusion) at 1 day, 1 week, and 1 month post-treatment: (1 day post-treatment value - BL pre-infusion value) (1 week post-treatment value - BL pre-infusion value) (1 month post-treatment value - BL pre-infusion value) |
| Change in Hospital Anxiety and Depression Scale (HADS) | 1 day, 1 week, and 1 month post-treatment from BL (pre-infusion) | The Hospital Anxiety and Depression Scale (HADS) consists of 14 items rated from 0-3 and 2 subscales Depression (7 items) and Anxiety (7 items). A higher score on each item represents more of each symptom (i.e., more depression or more anxiety). Each subscale score is the sum of the 7 items from each subscale. A score of 0-7 = Normal, 8-10=Borderline abnormal (borderline case), and 11-21=Abnormal (case). Change scores are calculated from baseline (pre-infusion) at 1 day, 1 week, and 1 month post-treatment: (1 day post-treatment value - BL pre-infusion value) (1 week post-treatment value - BL pre-infusion value) (1 month post-treatment value - BL pre-infusion value) |
Countries
United States
Participant flow
Pre-assignment details
Only 19 of the 20 enrolled started the study because one participant did not participate past consent.
Participants by arm
| Arm | Count |
|---|---|
| IV Lidocaine Then IV Diphenhydramine IV lidocaine dosed at 8mg/kg IV (maximum 500 mg) and infused over 30 minutes.
IV diphenhydramine 50mg total dosed as a 10mg IV bolus and then 40mg IV infusion over 30 minutes. | 10 |
| IV Diphenhydramine Then IV Lidocaine IV diphenhydramine 50mg total dosed as a 10mg IV bolus and then 40mg IV infusion over 30 minutes.
IV lidocaine dosed at 8mg/kg IV (maximum 500 mg) and infused over 30 minutes. | 9 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout (1 Month) | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | IV Lidocaine Then IV Diphenhydramine | IV Diphenhydramine Then IV Lidocaine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 19 Participants |
| Region of Enrollment United States | 10 participants | 9 participants | 19 participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 18 | 0 / 19 | 0 / 10 | 0 / 8 |
| serious Total, serious adverse events | 0 / 18 | 0 / 19 | 0 / 10 | 0 / 8 |
Outcome results
Primary
Change in Visual Analogue Scale (VAS)
Visual Analogue Scale (VAS) ranges from 0 (no pain) to 10 (the worse imaginable pain). Change scores are calculated from baseline (pre-infusion) at 15 minutes after start of infusion, 30 minutes after start of infusion, and 30 minutes after infusion complete: (15 minutes after start of infusion value - BL pre-infusion value) (30 minutes after start of infusion value - BL pre-infusion value) (30 minutes after infusion complete value - BL pre-infusion value)
Time frame: 15 minutes after start of infusion, 30 minutes after start of infusion, and 30 minutes after infusion complete from BL (pre-infusion)
Population: 2 participants in the IV Lidocaine arm are missing VAS 30 minutes after infusion started.~3 participants in the IV Lidocaine arm are missing VAS 30 minutes after infusion complete.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Lidocaine | Change in Visual Analogue Scale (VAS) | 15 minutes after start of infusion change | -2.6 units on a scale |
| IV Lidocaine | Change in Visual Analogue Scale (VAS) | 30 minutes after start of infusion change | -3.5 units on a scale |
| IV Lidocaine | Change in Visual Analogue Scale (VAS) | 30 minutes after infusion complete change | -3.6 units on a scale |
| IV Diphenhydramine | Change in Visual Analogue Scale (VAS) | 15 minutes after start of infusion change | -0.2 units on a scale |
| IV Diphenhydramine | Change in Visual Analogue Scale (VAS) | 30 minutes after start of infusion change | -1.5 units on a scale |
| IV Diphenhydramine | Change in Visual Analogue Scale (VAS) | 30 minutes after infusion complete change | -1.7 units on a scale |
Secondary
Change in Brief Pain Inventory (BPI): Pain on Average
The Pain on Average score in the Brief Pain Inventory is rated from 0-10, where 0 is no pain, and 10 is pain as bad as you can imagine. Change scores are calculated from baseline (pre-infusion) at 1 day, 1 week, and 1 month post-treatment: (1 day post-treatment value - BL pre-infusion value) (1 week post-treatment value - BL pre-infusion value) (1 month post-treatment value - BL pre-infusion value)
Time frame: 1 day, 1 week, and 1 month post-treatment from BL (pre-infusion)
Population: In the IV diphenhydramine arm 1 pt is missing BPI avg pain score at 1 week, and 2 are missing scores at 1 month. In the IV Lidocaine arm 1 pt is missing a score at 1 day, 1 is missing a score at 1 week, and 4 are missing scores at 1 month.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Lidocaine | Change in Brief Pain Inventory (BPI): Pain on Average | 1 day change from BL | -2 units on a scale |
| IV Lidocaine | Change in Brief Pain Inventory (BPI): Pain on Average | 1 week change from BL | -2 units on a scale |
| IV Lidocaine | Change in Brief Pain Inventory (BPI): Pain on Average | 1 month change from BL | -1 units on a scale |
| IV Diphenhydramine | Change in Brief Pain Inventory (BPI): Pain on Average | 1 day change from BL | 0 units on a scale |
| IV Diphenhydramine | Change in Brief Pain Inventory (BPI): Pain on Average | 1 week change from BL | 0 units on a scale |
| IV Diphenhydramine | Change in Brief Pain Inventory (BPI): Pain on Average | 1 month change from BL | -1 units on a scale |
Secondary
Change in Hospital Anxiety and Depression Scale (HADS)
The Hospital Anxiety and Depression Scale (HADS) consists of 14 items rated from 0-3 and 2 subscales Depression (7 items) and Anxiety (7 items). A higher score on each item represents more of each symptom (i.e., more depression or more anxiety). Each subscale score is the sum of the 7 items from each subscale. A score of 0-7 = Normal, 8-10=Borderline abnormal (borderline case), and 11-21=Abnormal (case). Change scores are calculated from baseline (pre-infusion) at 1 day, 1 week, and 1 month post-treatment: (1 day post-treatment value - BL pre-infusion value) (1 week post-treatment value - BL pre-infusion value) (1 month post-treatment value - BL pre-infusion value)
Time frame: 1 day, 1 week, and 1 month post-treatment from BL (pre-infusion)
Population: In the IV diphenhydramine arm 1 pt is missing HADS scores at 1 week, and 3 pts are missing scores at 1 month. In the IV Lidocaine arm 3 pts are missing HADS scores at 1 month.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Lidocaine | Change in Hospital Anxiety and Depression Scale (HADS) | Anxiety 1 day change | -1 units on a scale |
| IV Lidocaine | Change in Hospital Anxiety and Depression Scale (HADS) | Anxiety 1 week change | -1 units on a scale |
| IV Lidocaine | Change in Hospital Anxiety and Depression Scale (HADS) | Anxiety 1 month change | 0 units on a scale |
| IV Lidocaine | Change in Hospital Anxiety and Depression Scale (HADS) | Depression 1 day change | -0.5 units on a scale |
| IV Lidocaine | Change in Hospital Anxiety and Depression Scale (HADS) | Depression 1 week change | -1 units on a scale |
| IV Lidocaine | Change in Hospital Anxiety and Depression Scale (HADS) | Depression 1 month change | -1 units on a scale |
| IV Diphenhydramine | Change in Hospital Anxiety and Depression Scale (HADS) | Depression 1 week change | -2 units on a scale |
| IV Diphenhydramine | Change in Hospital Anxiety and Depression Scale (HADS) | Anxiety 1 day change | 0 units on a scale |
| IV Diphenhydramine | Change in Hospital Anxiety and Depression Scale (HADS) | Depression 1 day change | 0 units on a scale |
| IV Diphenhydramine | Change in Hospital Anxiety and Depression Scale (HADS) | Anxiety 1 week change | -2 units on a scale |
| IV Diphenhydramine | Change in Hospital Anxiety and Depression Scale (HADS) | Depression 1 month change | -0.5 units on a scale |
| IV Diphenhydramine | Change in Hospital Anxiety and Depression Scale (HADS) | Anxiety 1 month change | -1.0 units on a scale |
Secondary
Change in Short Form McGill Pain Questionnaire 2
Short-form McGill Pain Questionnaire version 2 consists of 22 pain items (Throbbing, Shooting, Stabbing, Sharp, Cramping, Gnawing, Hot-burning, Aching, Heavy, Tender, Splitting, Tiring-exhausting, Sickening, Fearful, Punishing-cruel, Electric-shock, Cold-freezing, Piercing, Pain caused by light touch, Itching, Tingling or 'pins and needles', and Numbness). Each item is rated on a scale from 0-10, where 0=none, and 10=worst possible pain. The total pain score is the sum of these 22 items, ranging from 0-220. Change scores are calculated from baseline (pre-infusion) at 30 minutes, 1 week, and 1 month post-treatment: (30 minutes post-treatment value - BL pre-infusion value) (1 week post-treatment value - BL pre-infusion value) (1 month post-treatment value - BL pre-infusion value)
Time frame: 30 minutes, 1 week, and 1 month post-treatment from BL (pre-infusion)
Population: 1. participant in the IV diphenhydramine arm is missing SFMPQ total score 1 week post-treatment.~2. participants in the IV diphenhydramine arm are missing SFMPQ total score 1 month post-treatment.~3. participants in the IV Lidocaine arm are missing SFMPQ total score 1 month post-treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| IV Lidocaine | Change in Short Form McGill Pain Questionnaire 2 | 30 minutes change from BL | -14.5 units on a scale |
| IV Lidocaine | Change in Short Form McGill Pain Questionnaire 2 | 1 week change from BL | -18 units on a scale |
| IV Lidocaine | Change in Short Form McGill Pain Questionnaire 2 | 1 month change from BL | 4 units on a scale |
| IV Diphenhydramine | Change in Short Form McGill Pain Questionnaire 2 | 30 minutes change from BL | -15 units on a scale |
| IV Diphenhydramine | Change in Short Form McGill Pain Questionnaire 2 | 1 week change from BL | -17 units on a scale |
| IV Diphenhydramine | Change in Short Form McGill Pain Questionnaire 2 | 1 month change from BL | -18 units on a scale |