Effect of Neurokinin-1 Receptor (NK1R) Antagonism on Pruritus in Patients With Sezary Syndrome

• Sponsor: Vanderbilt University Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01625455
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arms: 2
• Duration (Months): 53
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this randomized, double-blinded, placebo-controlled study is to test the hypothesis that administration of aprepitant will decrease the severity of pruritus in patients with Sèzary Syndrome.

Condition or Disease	Intervention/Treatment	Phase
Sezary Syndrome; Pruritus	Drug: Aprepitant; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Neurokinin-1 Receptor (NK1R) Antagonism on Pruritus in Patients With Sezary Syndrome
• Study Start Date: Feb 1, 2012
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Aprepitant Aprepitant will be given orally in a dose of 125mg on day 1 and 80mg daily on each subsequent day for a total of 7 days.	Drug: Aprepitant; Aprepitant will be given orally in a dose of 125mg on day 1 and 80mg daily on each subsequent day for a total of 7 days.; Other Names: Emend
Placebo Comparator: Placebo Matching placebo will be given in place of aprepitant	Drug: Placebo; Placebo will be given orally for a total of 7 days.

Outcome Measures

Primary Outcome Measures

1. Severity of Pruritus [one week]

   The primary endpoint is the severity of pruritus as measured on the visual analogue scale. A score of 100 indicated the worst pruritus imaginable, while 0 indicated no pruritus.

Secondary Outcome Measures

1. Quality of Life [one week]

   The secondary endpoint is the quality of life as measured on the Dermatology Quality of Life Index (DLQI). For a series of 10 questions the responses are scored: Very much, scored 3; A lot, scored 2; A little, scored 1; Not at all, scored 0; Not relevant, scored 0; and Question unanswered, scored 0. The scores are summed and the larger the score the greater the effect of the dermatological disease impact on quality of life. Maximum response for all ten questions 30, minimum 0.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Known Sezary Syndrome

• Pruritus uncontrolled by conventional treatment. Baseline visual analogue scale > 4.

• Age 18 through 80 years of age.

• Stable medication regimens for both Sezary Syndrome and pruritus for 3 months prior to study participation.

Exclusion Criteria:

• Known hepatic impairment (defined as liver function tests >3 times the upper limit of normal).

• Pregnancy (all women of child-bearing potential will undergo urine beta-hcg testing).

• Concurrent use of pimozide, terfenadine, astemizole, or cisapride.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37235

Sponsors and Collaborators

• Vanderbilt University Medical Center

Investigators

• Principal Investigator: Nancy J Brown, MD, Vanderbilt University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ahmad S, Wang L, Ward PE. Dipeptidyl(amino)peptidase IV and aminopeptidase M metabolize circulating substance P in vivo. J Pharmacol Exp Ther. 1992 Mar;260(3):1257-61.
• Bernengo MG, Novelli M, Quaglino P, Lisa F, De Matteis A, Savoia P, Cappello N, Fierro MT. The relevance of the CD4+ CD26- subset in the identification of circulating Sézary cells. Br J Dermatol. 2001 Jan;144(1):125-35.
• Booken N, Heck M, Nicolay JP, Klemke CD, Goerdt S, Utikal J. Oral aprepitant in the therapy of refractory pruritus in erythrodermic cutaneous T-cell lymphoma. Br J Dermatol. 2011 Mar;164(3):665-7. doi: 10.1111/j.1365-2133.2010.10108.x. Epub 2011 Jan 28.
• Cevikbas F, Steinhoff M, Ikoma A. Role of spinal neurotransmitter receptors in itch: new insights into therapies and drug development. CNS Neurosci Ther. 2011 Dec;17(6):742-9. doi: 10.1111/j.1755-5949.2010.00201.x. Epub 2010 Oct 15. Review.
• Duval A, Dubertret L. Aprepitant as an antipruritic agent? N Engl J Med. 2009 Oct 1;361(14):1415-6. doi: 10.1056/NEJMc0906670.
• Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med. 2008 Jun 5;358(23):2482-94. doi: 10.1056/NEJMra0706547. Review.
• Heymann E, Mentlein R. Liver dipeptidyl aminopeptidase IV hydrolyzes substance P. FEBS Lett. 1978 Jul 15;91(2):360-4.
• Lambeir AM, Durinx C, Scharpé S, De Meester I. Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci. 2003 Jun;40(3):209-94. Review.
• Mussap CJ, Geraghty DP, Burcher E. Tachykinin receptors: a radioligand binding perspective. J Neurochem. 1993 Jun;60(6):1987-2009. Review.
• Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, Zackheim H, Duvic M, Estrach T, Lamberg S, Wood G, Dummer R, Ranki A, Burg G, Heald P, Pittelkow M, Bernengo MG, Sterry W, Laroche L, Trautinger F, Whittaker S; ISCL/EORTC. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007 Sep 15;110(6):1713-22. Epub 2007 May 31. Review. Erratum in: Blood. 2008 May 1;111(9):4830.
• Vonderheid EC, Bernengo MG, Burg G, Duvic M, Heald P, Laroche L, Olsen E, Pittelkow M, Russell-Jones R, Takigawa M, Willemze R; ISCL. Update on erythrodermic cutaneous T-cell lymphoma: report of the International Society for Cutaneous Lymphomas. J Am Acad Dermatol. 2002 Jan;46(1):95-106. Review.

• Responsible Party: Nancy J. Brown, Chair and Physician-in-chief, Department of Medicine, Hugh Jackson Morgan Professor Medicine and Pharmacology, Vanderbilt University School of Medicine, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT01625455
• Other Study ID Numbers: 110806
• First Posted: Jun 21, 2012
• Last Update Posted: May 10, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Nancy J. Brown, Chair and Physician-in-chief, Department of Medicine, Hugh Jackson Morgan Professor Medicine and Pharmacology, Vanderbilt University School of Medicine, Vanderbilt University: Sezary Syndrome; Pruritus; Aprepitant; Neurokinin-1
• Additional relevant MeSH terms: Sezary Syndrome; Pruritus; Syndrome; Aprepitant

Study Results

Participant Flow

Pre-assignment Detail	Seven subjects were consented and enrolled. Two did not meet inclusion/exclusion criteria and were not randomized.

Arm/Group Title	Placebo Then Aprepitant	Aprepitant Then Placebo.
Arm/Group Description	These subjects received placebo during the first week and then crossed over to aprepitant for the second week.	These subjects received aprepitant during the first week and then crossed over to placebo for the second week.
Period Title: Overall Study
STARTED	2	3
COMPLETED	2	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo Then Aprepitant	Aprepitant Then Placebo.	Total
Arm/Group Description	These subjects received placebo during the first week and then crossed over to aprepitant for the second week.	These subjects received aprepitant during the first week and then crossed over to placebo for the second week.	Total of all reporting groups
Overall Participants	2	3	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	2 66.7%	2 40%
>=65 years	2 100%	1 33.3%	3 60%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	71	58.3	63.4
Sex: Female, Male (Count of Participants)
Female	1 50%	2 66.7%	3 60%
Male	1 50%	1 33.3%	2 40%
Region of Enrollment (participants) [Number]
United States	2 100%	3 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	Severity of Pruritus
Description	The primary endpoint is the severity of pruritus as measured on the visual analogue scale. A score of 100 indicated the worst pruritus imaginable, while 0 indicated no pruritus.
Time Frame	one week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aprepitant	Placebo
Arm/Group Description	Aprepitant will be given orally in a dose of 125mg on day 1 and 80mg daily on each subsequent day for a total of 7 days. Aprepitant: Aprepitant will be given orally in a dose of 125mg on day 1 and 80mg daily on each subsequent day for a total of 7 days.	Matching placebo will be given in place of aprepitant Placebo: Placebo will be given orally for a total of 7 days.
Measure Participants	5	5
Mean (Standard Deviation) [units on a scale]	58.20 (17.82)	47.47 (20.22)

2. Secondary Outcome

Title	Quality of Life
Description	The secondary endpoint is the quality of life as measured on the Dermatology Quality of Life Index (DLQI). For a series of 10 questions the responses are scored: Very much, scored 3; A lot, scored 2; A little, scored 1; Not at all, scored 0; Not relevant, scored 0; and Question unanswered, scored 0. The scores are summed and the larger the score the greater the effect of the dermatological disease impact on quality of life. Maximum response for all ten questions 30, minimum 0.
Time Frame	one week

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aprepitant	Placebo
Arm/Group Description	Aprepitant will be given orally in a dose of 125mg on day 1 and 80mg daily on each subsequent day for a total of 7 days. Aprepitant: Aprepitant will be given orally in a dose of 125mg on day 1 and 80mg daily on each subsequent day for a total of 7 days.	Matching placebo will be given in place of aprepitant Placebo: Placebo will be given orally for a total of 7 days.
Measure Participants	5	5
Mean (Standard Deviation) [scores on a scale]	14.2 (9.7)	14.8 (10.3)

Adverse Events

Arm/Group Title	Placebo		Aprepitant
Arm/Group Description
All Cause Mortality
	Placebo		Aprepitant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Serious Adverse Events
	Placebo		Aprepitant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Aprepitant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.