Study of Promethazine for Treatment of Diabetic Gastroparesis

• Sponsor: Dartmouth-Hitchcock Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02130622
• Collaborator: American College of Gastroenterology (Other)
• Enrollment: 3
• Location: 1
• Arms: 2
• Actual Duration (Months): 10.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Gastroparesis	Drug: Promethazine; Drug: Sugar pill	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pilot, Randomized, Double-blind, Placebo-controlled Trial of Promethazine for Treatment of Diabetic Gastroparesis.
• Actual Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: May 14, 2015
• Actual Study Completion Date: May 14, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Promethazine Promethazine 12.5 mg P.O. t.i.d. for 4 weeks	Drug: Promethazine; Other Names: Phenergan
Placebo Comparator: Sugar Pill Placebo P.O. t.i.d. for 4 weeks	Drug: Sugar pill; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

1. Occurrence of Adverse Events [4 weeks]

2. Use of Rescue Medication [4 weeks]

   Frequency of use of the "rescue medication" meclizine

3. The Impact on Work Activity as Measured by the Work Productivity and Activity Impairment Questionnaire. (WPAI). [4 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756

Sponsors and Collaborators

• Dartmouth-Hitchcock Medical Center
• American College of Gastroenterology

Investigators

• Principal Investigator: Brian E. Lacy, MD, Dartmouth-Hitchcock Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• Janssen P, Harris MS, Jones M, Masaoka T, Farré R, Törnblom H, Van Oudenhove L, Simrén 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. Review.
• 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.
• McHugh S, Lico S, Diamant NE. Cisapride vs metoclopramide. An acute study in diabetic gastroparesis. Dig Dis Sci. 1992 Jul;37(7):997-1001.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Wahlqvist P, Carlsson J, Stålhammar 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.

• Responsible Party: Dartmouth-Hitchcock Medical Center
• ClinicalTrials.gov Identifier: NCT02130622
• Other Study ID Numbers: D14076
• First Posted: May 5, 2014
• Last Update Posted: Aug 7, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Dartmouth-Hitchcock Medical Center: Diabetic Gastroparesis; Promethazine
• Additional relevant MeSH terms: Gastroparesis; Promethazine; Diphenhydramine

Study Results

Participant Flow

Recruitment Details	Participants were recruited from the gastroenterology clinic at Dartmouth-Hitchcock Medical Center at the time of routine appointments.

Arm/Group Title	Promethazine	Sugar Pill
Arm/Group Description	Promethazine 12.5 mg P.O. t.i.d. for 4 weeks Promethazine	Placebo P.O. t.i.d. for 4 weeks Sugar pill
Period Title: Overall Study
STARTED	2	1
COMPLETED	2	1
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Promethazine	Sugar Pill	Total
Arm/Group Description	Promethazine 12.5 mg P.O. t.i.d. for 4 weeks Promethazine	Placebo P.O. t.i.d. for 4 weeks Sugar pill	Total of all reporting groups
Overall Participants	2	1	3
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	1 100%	3 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 100%	1 100%	3 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	2 100%	1 100%	3 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	2 100%	1 100%	3 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	2 100%	1 100%	3 100%

Outcome Measures

1. Primary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Insufficient recruitment resulting in insufficient data to analyze

Arm/Group Title	Promethazine	Sugar Pill
Arm/Group Description	Promethazine 12.5 mg P.O. t.i.d. for 4 weeks Promethazine	Placebo P.O. t.i.d. for 4 weeks Sugar pill
Measure Participants	0	0

2. Secondary Outcome

Title	Occurrence of Adverse Events
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Insufficient recruitment resulting in insufficient data to analyze

Arm/Group Title	Promethazine	Sugar Pill
Arm/Group Description	Promethazine 12.5 mg P.O. t.i.d. for 4 weeks Promethazine	Placebo P.O. t.i.d. for 4 weeks Sugar pill
Measure Participants	0	0

3. Secondary Outcome

Title	Use of Rescue Medication
Description	Frequency of use of the "rescue medication" meclizine
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Data not collected

Arm/Group Title	Promethazine	Sugar Pill
Arm/Group Description	Promethazine 12.5 mg P.O. t.i.d. for 4 weeks Promethazine	Placebo P.O. t.i.d. for 4 weeks Sugar pill
Measure Participants	0	0

4. Secondary Outcome

Title	The Impact on Work Activity as Measured by the Work Productivity and Activity Impairment Questionnaire. (WPAI).
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Insufficient recruitment resulting in insufficient data to analyze

Arm/Group Title	Promethazine	Sugar Pill
Arm/Group Description	Promethazine 12.5 mg P.O. t.i.d. for 4 weeks Promethazine	Placebo P.O. t.i.d. for 4 weeks Sugar pill
Measure Participants	0	0

Adverse Events

Time Frame	From date of ICF signature through study completion, approximately 5 weeks
Arm/Group Title	Promethazine		Sugar Pill
Arm/Group Description	Promethazine 12.5 mg P.O. t.i.d. for 4 weeks Promethazine		Placebo P.O. t.i.d. for 4 weeks Sugar pill
All Cause Mortality
	Promethazine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Serious Adverse Events
	Promethazine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Promethazine		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		0/1 (0%)
Cardiac disorders
Chest Pain	1/2 (50%)	1	0/1 (0%)	0
Psychiatric disorders
Auditory Hallucinations	1/2 (50%)	2	0/1 (0%)	0
Nightmares	1/2 (50%)	3	0/1 (0%)	0

Limitations/Caveats

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

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.