Study of Promethazine for Treatment of Diabetic Gastroparesis

NCT02130622 | Terminated Phase 2 Results

• 1 other identifier: D14076
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetic Gastroparesis

Keywords

Diabetic Gastroparesis; Promethazine

Outcome Measures

Primary Outcomes (1)

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

  4 weeks

Secondary Outcomes (3)

• Occurrence of Adverse Events

  4 weeks

• Use of Rescue Medication

  4 weeks

• The Impact on Work Activity as Measured by the Work Productivity and Activity Impairment Questionnaire. (WPAI).

  4 weeks

Study Arms (2)

Promethazine

EXPERIMENTAL

Promethazine 12.5 mg P.O. t.i.d. for 4 weeks

Drug: Promethazine

Sugar Pill

PLACEBO COMPARATOR

Placebo P.O. t.i.d. for 4 weeks

Drug: Sugar pill

Interventions

Promethazine DRUG

Also known as: Phenergan

Promethazine

Sugar pill DRUG

Also known as: Placebo

Sugar Pill

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead
• American College of Gastroenterology: collaborator

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Related Publications (17)

• Cherian D, Parkman HP. Nausea and vomiting in diabetic and idiopathic gastroparesis. Neurogastroenterol Motil. 2012 Mar;24(3):217-22, e103. doi: 10.1111/j.1365-2982.2011.01828.x. Epub 2011 Nov 27.

  PMID: 22118574 BACKGROUND

• Janssen P, Harris MS, Jones M, Masaoka T, Farre R, Tornblom H, Van Oudenhove L, Simren M, Tack J. The relation between symptom improvement and gastric emptying in the treatment of diabetic and idiopathic gastroparesis. Am J Gastroenterol. 2013 Sep;108(9):1382-91. doi: 10.1038/ajg.2013.118.

  PMID: 24005344 BACKGROUND

• Ricci DA, Saltzman MB, Meyer C, Callachan C, McCallum RW. Effect of metoclopramide in diabetic gastroparesis. J Clin Gastroenterol. 1985 Feb;7(1):25-32. doi: 10.1097/00004836-198502000-00003.

  PMID: 3884697 BACKGROUND

• McCallum RW, Ricci DA, Rakatansky H, Behar J, Rhodes JB, Salen G, Deren J, Ippoliti A, Olsen HW, Falchuk K, et al. A multicenter placebo-controlled clinical trial of oral metoclopramide in diabetic gastroparesis. Diabetes Care. 1983 Sep-Oct;6(5):463-7. doi: 10.2337/diacare.6.5.463.

  PMID: 6400707 BACKGROUND

• Perkel MS, Moore C, Hersh T, Davidson ED. Metoclopramide therapy in patients with delayed gastric emptying: a randomized, double-blind study. Dig Dis Sci. 1979 Sep;24(9):662-6. doi: 10.1007/BF01314461.

  PMID: 385260 BACKGROUND

• Snape WJ Jr, Battle WM, Schwartz SS, Braunstein SN, Goldstein HA, Alavi A. Metoclopramide to treat gastroparesis due to diabetes mellitus: a double-blind, controlled trial. Ann Intern Med. 1982 Apr;96(4):444-6. doi: 10.7326/0003-4819-96-4-444.

  PMID: 7065559 BACKGROUND

• Patterson D, Abell T, Rothstein R, Koch K, Barnett J. A double-blind multicenter comparison of domperidone and metoclopramide in the treatment of diabetic patients with symptoms of gastroparesis. Am J Gastroenterol. 1999 May;94(5):1230-4. doi: 10.1111/j.1572-0241.1999.00456.x.

  PMID: 10235199 BACKGROUND

• Erbas T, Varoglu E, Erbas B, Tastekin G, Akalin S. Comparison of metoclopramide and erythromycin in the treatment of diabetic gastroparesis. Diabetes Care. 1993 Nov;16(11):1511-4. doi: 10.2337/diacare.16.11.1511.

  PMID: 8299441 BACKGROUND

• McHugh S, Lico S, Diamant NE. Cisapride vs metoclopramide. An acute study in diabetic gastroparesis. Dig Dis Sci. 1992 Jul;37(7):997-1001. doi: 10.1007/BF01300277.

  PMID: 1618070 BACKGROUND

• Feldman M, Smith HJ. Effect of cisapride on gastric emptying of indigestible solids in patients with gastroparesis diabeticorum. A comparison with metoclopramide and placebo. Gastroenterology. 1987 Jan;92(1):171-4. doi: 10.1016/0016-5085(87)90854-7.

  PMID: 3781184 BACKGROUND

• 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.

  PMID: 23735907 BACKGROUND

• 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.

  PMID: 20410771 BACKGROUND

• 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.

  PMID: 18304050 BACKGROUND

• 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. doi: 10.1046/j.1365-2036.2003.01612.x.

  PMID: 12848636 BACKGROUND

• 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.

  PMID: 22284754 BACKGROUND

• Reilly MC, Bracco A, Ricci JF, Santoro J, Stevens T. The validity and accuracy of the Work Productivity and Activity Impairment questionnaire--irritable bowel syndrome version (WPAI:IBS). Aliment Pharmacol Ther. 2004 Aug 15;20(4):459-67. doi: 10.1111/j.1365-2036.2004.02091.x.

  PMID: 15298641 BACKGROUND

• Wahlqvist P, Carlsson J, Stalhammar NO, Wiklund I. Validity of a Work Productivity and Activity Impairment questionnaire for patients with symptoms of gastro-esophageal reflux disease (WPAI-GERD)--results from a cross-sectional study. Value Health. 2002 Mar-Apr;5(2):106-13. doi: 10.1046/j.1524-4733.2002.52101.x.

  PMID: 11918826 BACKGROUND

MeSH Terms

Interventions

Promethazine; Sugars

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Phenothiazines; Sulfur Compounds; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Carbohydrates

Limitations and Caveats

Insufficient enrollment to provide study results. Study terminated before full enrollment due to lack of participant interest.

Results Point of Contact

• Title: Gastroenterology Research Team Lead
• Organization: Dartmouth-Hitchcock

Jessica.I.Chevalier@hitchcock.org

603-653-9033

Study Officials

• Brian E. Lacy, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2014
• First Posted: May 5, 2014
• Study Start: July 1, 2014
• Primary Completion: May 14, 2015
• Study Completion: May 14, 2015
• Last Updated: August 7, 2018
• Results First Posted: May 17, 2018

Record last verified: 2018-07

Locations

US (1)