Randomized Trial of the Effectiveness of Topical ABH Gel vs. Placebo in Cancer Patients With Nausea

Study Overview
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Brief Summary
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This randomized clinical trial studies ABH (lorazepam, diphenhydramine hydrochloride, and haloperidol) gel in patients with nausea. ABH gel, when absorbed into the skin, may be an effective treatment for nausea and vomiting. The general purpose of this research study is to improve the treatment of nausea and vomiting.

Detailed Description
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PRIMARY OBJECTIVES: I. The primary outcome is the change in numeric rating scale in self-reported nausea on a 0-10 scale from baseline to 60 minutes of treatment. OUTLINE: All individuals who are eligible are randomized to a sequence of treatments: either placebo-ABH or ABH-placebo. The randomization list will be generated by the Study Biostatistician. Neither the patient nor the investigator will have knowledge of the actual content of Drug A or B, so the study will be double-blinded, and placebo controlled. Drug A: The dose of the drugs in the 1.0 mL dose will be 2 mg of lorazepam, 25 mg of diphenhydramine, and 2 mg of haloperidol in a pluronic lecithin organogel. It will be rubbed on the volar surface of the wrists by the subject, for 2 minutes as done in clinical practice, at time 0. Drug B: equivalent but no ABH. Subjects will rub 1 mL of the first drug, Drug A gel, between their wrists for 2 minutes. Subjects will be asked to rate and complete their nausea on the Memorial Symptom Assessment Scale (CMSAS). At time 60 two options can occur. One, if there is no effect after the first drug in one hour, then patients will receive the second drug. If there is no effect in one hour from second drug, patients will stop the study and resume normal treatment for their nausea. Or two, if the first gel reduces nausea by more than 1 point on the 0-10 scale, subjects will wait 4 hours to apply the next gel. At this point, the study procedures will be repeated. After treatment, patients are followed up for up to 8 hours. Subjects will be asked to rate their nausea on a 0 (no nausea) to 10 (worst possible nausea) scale at baseline, 60, 120, 180, and 240 minutes. Subjects will complete the Memorial Symptom Assessment Scale (CMSAS), a reliable and valid instrument for assessing relevant symptoms including lack of energy, lack of appetite, pain, dry mouth, weight loss, feeling drowsy, shortness of breath, constipation, difficulty sleeping, difficulty concentrating, and nausea.

Official Title
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A Randomized Trial of the Effectiveness of Topical ABH Gel (Ativan®, Lorazepam; Benadryl®, Diphenhydramine; and Haldol®, Haloperidol Gel) Versus Placebo in Patients With Nausea

Conditions
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Nausea, Vomiting

Intervention / Treatment
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* Drug: ABH gel
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: English speaking No allergies to the drugs Able to complete the forms If a woman of childbearing age, agree to use contraception; women will be offered a pregnancy test before doing the trial if they request one, as stated in the Informed Consent Form Patients must have a self reported nausea score of at least 4 on a numeric rating scale of 0-10 (zero being no nausea and ten being the worst possible nausea); patients are not required to have vomiting Patients must have had or have cancer, or have had a consultation with the palliative care team They must not have had any changes to their nausea program within the past 12 hours, if on anti-emetics Patients must not have received chemotherapy within 5 days, unless it is a stable oral chemotherapy drug such as capecitabine (Xeloda), erlotinib (Tarceva), or similar Exclusion Criteria: History of substance abuse, psychiatric disorder, acquired brain injury, the possibility of pregnancy (not using birth control, and of child bearing age) Use of any medication that would contraindicate benzodiazepine administration Pregnant or nursing Children

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo then ABH<br>All subjects randomized to two sequences of treatments: either placebo-ABH or ABH-placebo. All participants will receive both drug A and drug B. After applying gel, Drug A or B, on wrists for 2 minutes, time 0. From baseline to 60 minutes of treatment two options will occur. At 60 minutes, if patients have at least 1 point reduction in their nausea score, they must wait 4 hours before switching to opposite drug. After administration of drug, the study procedures will be repeated. Or, at 60 minutes, if no change or increase in nausea score has been recorded, alternative treatment will be given. If the second treatment is ineffective at one hour (total time 2 hours) then alternative usual medications will be given. After completion of study treatment, patients are followed up for up to 8 hours. | Drug: ABH gel<br>* Given topically<br>* Other names: R-1625;Other: placebo<br>* Given topically<br>* Other names: PLCB;|
| Experimental: ABH then placebo<br>All subjects randomized to two sequences of treatments: either placebo-ABH or ABH-placebo. All participants will receive both drug A and drug B. After applying gel, Drug A or B, on wrists for 2 minutes, time 0. From baseline to 60 minutes of treatment two options will occur. At 60 minutes, if patients have at least 1 point reduction in their nausea score, they must wait 4 hours before switching to opposite drug. After administration of drug, the study procedures will be repeated. Or, at 60 minutes, if no change or increase in nausea score has been recorded, alternative treatment will be given. If the second treatment is ineffective at one hour (total time 2 hours) then alternative usual medications will be given. After completion of study treatment, patients are followed up for up to 8 hours. | Drug: ABH gel<br>* Given topically<br>* Other names: R-1625;Other: placebo<br>* Given topically<br>* Other names: PLCB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in Numeric Rating Scale in Self-reported Nausea From Baseline Minus 60 Minutes of Treatment. | The outcome measure for change was calculated from value at baseline minus value at 60 minutes. Subjects were asked to rate their nausea on a 0 (no nausea) to 10 (worst possible nausea) scale. Subjects who were eligible were randomly assigned to two sequences: one sequence used ABH gel first and then placebo; and the other sequence used placebo first and then ABH gel. We assumed that there was no carry-over effect from the first treatment to the second. A paired t-test was used to compare if ABH gel is not better than the placebo gel. A repeated measure analysis was used to compare the two treatment sequences. This endpoint was chosen as the drug gel because it is typically used as a prn (as needed) gel in actual practice, when relief is needed in short order. | 60 minutes after application |