Study of Promethazine for Treatment of Diabetic Gastroparesis

Overview

Adult diabetic patients (ages 18-65) with gastric emptying scintigraphy-confirmed delayed gastric emptying will be recruited to participate in the study. Using double-blinded methodology, study participants will be randomly assigned to one of two treatment arms: promethazine 12.5 mg three times daily for 28 days or placebo three times daily for 28 days. The primary outcome will be the change in gastroparesis symptom severity, as measured by the Gastroparesis Cardinal Symptom Index (GCSI) at four weeks compared to baseline. Participants will be seen for a clinic evaluation at weeks 0, 2 and 4, during which symptom scores, adverse events and treatment compliance will be assessed. It is hypothesized promethazine treatment will be superior to placebo in improving symptoms of gastroparesis.

Full Title of Study: “A Pilot, Randomized, Double-blind, Placebo-controlled Trial of Promethazine for Treatment of Diabetic Gastroparesis.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: May 14, 2015

Interventions

  • Drug: Promethazine
  • Drug: Sugar pill

Arms, Groups and Cohorts

  • Experimental: Promethazine
    • Promethazine 12.5 mg P.O. t.i.d. for 4 weeks
  • Placebo Comparator: Sugar Pill
    • Placebo P.O. t.i.d. for 4 weeks

Clinical Trial Outcome Measures

Primary Measures

  • Change in Patient-reported Symptoms as Measured by the Gastroparesis Cardinal Symptom Index Score (GCSI, 14) From Week 0 to Week 4.
    • Time Frame: 4 weeks

Secondary Measures

  • Occurrence of Adverse Events
    • Time Frame: 4 weeks
  • Use of Rescue Medication
    • Time Frame: 4 weeks
    • Frequency of use of the “rescue medication” meclizine
  • The Impact on Work Activity as Measured by the Work Productivity and Activity Impairment Questionnaire. (WPAI).
    • Time Frame: 4 weeks

Participating in This Clinical Trial

Inclusion Criteria

  • adult patients 18-65 years of age – clinical diagnosis of diabetic gastroparesis. – EGD without evidence of gastric outlet obstruction within the past five years – gastric emptying scintigraphy test demonstrating >10% solid food retention at 4 hours within the past three years. Exclusion Criteria:

  • the inability or unwillingness to provide informed consent – currently pregnant or breast feeding – prior placement of a gastric stimulator – pyloric botulinum toxin injection within the past 12 months – prior gastric surgery – history of a connective tissue disorder – use of narcotic medication within the past four weeks – hemoglobin A1C >12 mg/dL within the past 3 months – current or recent (within past 4 weeks) use of promethazine, metoclopramide or domperidone – hypersensitivity or prior adverse reaction to promethazine – concomitant use of phenothiazines (i.e. prochlorperazine, chlorpromazine) or other agents likely to increase extrapyramidal reactions – concomitant use of tiotropium or ipratropium – narrow angle glaucoma – urinary retention – Parkinson's disease – significant psychiatric disease – history of seizure.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Dartmouth-Hitchcock Medical Center
  • Collaborator
    • American College of Gastroenterology
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Brian E. Lacy, MD, Principal Investigator, Dartmouth-Hitchcock Medical Center

References

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Ehrenpreis ED, Deepak P, Sifuentes H, Devi R, Du H, Leikin JB. The metoclopramide black box warning for tardive dyskinesia: effect on clinical practice, adverse event reporting, and prescription drug lawsuits. Am J Gastroenterol. 2013 Jun;108(6):866-72. doi: 10.1038/ajg.2012.300.

Tan PC, Khine PP, Vallikkannu N, Omar SZ. Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2010 May;115(5):975-981. doi: 10.1097/AOG.0b013e3181d99290.

Braude D, Crandall C. Ondansetron versus promethazine to treat acute undifferentiated nausea in the emergency department: a randomized, double-blind, noninferiority trial. Acad Emerg Med. 2008 Mar;15(3):209-15. doi: 10.1111/j.1553-2712.2008.00060.x.

Revicki DA, Rentz AM, Dubois D, Kahrilas P, Stanghellini V, Talley NJ, Tack J. Development and validation of a patient-assessed gastroparesis symptom severity measure: the Gastroparesis Cardinal Symptom Index. Aliment Pharmacol Ther. 2003 Jul 1;18(1):141-50.

Revicki DA, Camilleri M, Kuo B, Szarka LA, McCormack J, Parkman HP. Evaluating symptom outcomes in gastroparesis clinical trials: validity and responsiveness of the Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD). Neurogastroenterol Motil. 2012 May;24(5):456-63, e215-6. doi: 10.1111/j.1365-2982.2012.01879.x. Epub 2012 Jan 27.

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