Qbrexza Cloths for Hyperhidrosis of Amputation Sites

• ClinicalTrials.gov Identifier: NCT04924036
• Recruitment Status: Recruiting
• First Posted: June 11, 2021
• Last Update Posted: February 10, 2022
• Sponsor: University of Utah
• Information provided by (Responsible Party): Stephanie Z Klein, University of Utah

Study Description

Brief Summary:

This is a Prospective, Double Blinded, Placebo Controlled, Randomized, Cross-over trial using Qbrexza Cloths to treat hyperhidrosis of amputation sites. There is a 2 week screening period where patients will use an activity monitor to establish baseline activity level, then patients will be randomized to receive either Qbrexza cloths or placebo for 4 weeks, then a 2 week washout, and then a 4-week cross-over treatment period.

Condition or disease	Intervention/treatment	Phase
Amputation; Hyperhidrosis	Drug: glycopyrronium cloths; Drug: Placebo	Phase 2

Detailed Description:

BACKGROUND:

Approximately 1 in 190 people in the United States have experienced a limb amputation. Of these patients with amputations, over sixty percent suffer from hyperhidrosis at the amputation site. Amputation site hyperhidrosis interferes with these patients' daily activities as well as their ability to engage in vigorous activity beneficial to their overall health. In fact, amputees identified heat and sweating as what reduces their quality of life more than any other problem, even pain. Despite the significant impact hyperhidrosis has on amputees' quality of life and ability to stay physically active, there are no self-administered, non-invasive, well-tolerated treatments for amputation site hyperhidrosis. Botulinum toxin injections are an available treatment option for focal hyperhidrosis. However, the large surface area covered by the prosthetic and prosthetic sleeve often necessitates very large volumes of botulinum toxin for effective treatment at amputation sites. This is costly, making it difficult to be able to treat the entire affected area. Botulinum toxin also requires office visits and repeat treatments every 4-6 months.

Glycopyrronium cloths are a unique treatment possibility, because they can easily be used over a large body surface area and can easily be self-administered at home. At this time, glycopyrronium cloths are only FDA approved for use in the axillae. There are two primary differences between the use of these cloths at amputation sites and axillae: 1) the amputation site is occluded during daytime hours by the prosthetic and 2) the area treated for amputation-site hyperhidrosis (the entire area covered by the prosthetic sleeve) is typically a much larger surface area than the axillae. These factors could significantly increase systemic absorption of glycopyrronium and cause systemic side effects. In order to minimize these effects, the medication will be applied at night, when the site is not occluded. Frequent visits with the investigator will also encourage early reporting of symptoms which could be the result of systemic side effects associated with use on a larger surface area. Patient reported outcomes will be used to determine effectiveness.

This is a Prospective, Double Blinded, Placebo Controlled, Randomized, Cross-over trial.

Participants will be randomized, using a 1:1 ratio, to one of 2 arms:

• Arm #1: At Baseline participants will receive active treatment for 4 weeks, completing a 1 week wash out period and then concluding with 4 weeks of placebo treatment
• Arm #2: At baseline participants will receive placebo for 4 weeks, completing a 1 week washout period and then concluding with active treatment for 4 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: This is a Prospective, Double Blinded, Placebo Controlled, Randomized, Cross-over trial.
• Masking: Double (Participant, Investigator)
• Masking Description: Participants and investigators in the trial will be blinded.
• Primary Purpose: Treatment
• Official Title: A Prospective Trial to Assess How Glycopyrronium Cloths at the Amputation Site of Limb Amputees Changes the Severity of Hyperhidrosis and the Fit and Function of the Prosthetic Measured by Patient Reported Outcomes
• Actual Study Start Date: September 27, 2021
• Estimated Primary Completion Date: September 2, 2023
• Estimated Study Completion Date: September 1, 2024

Arms and Interventions

Arm	Intervention/treatment
Glycopyrronium Cloths then Placebo; Participants that are randomized to Glycopyrronium cloths for 4 weeks, then 2 week wash out, then cross over to placebo cloths for 4 weeks.	Drug: glycopyrronium cloths; Qbrexza is an anticholinergic indicated for topical treatment of axillary hyperhidrosis in adults and pediatric patients 9 years of age and older; Other Name: Qbrexza Cloths; Drug: Placebo; Placebo for this study are cloths that look like the qbrexza cloths but do not have any active ingredient.
Placebo then Glycopyrronium Cloths; Participants that are randomized to placebo cloths for 4 weeks, then 2 week wash out, then cross over to Glycopyrronium cloths for 4 weeks.	Drug: glycopyrronium cloths; Qbrexza is an anticholinergic indicated for topical treatment of axillary hyperhidrosis in adults and pediatric patients 9 years of age and older; Other Name: Qbrexza Cloths; Drug: Placebo; Placebo for this study are cloths that look like the qbrexza cloths but do not have any active ingredient.

Outcome Measures

Primary Outcome Measures :

1. Determine if daily use of glycopyrronium cloths applied to the amputation site decreases hyperhidrosis severity and improved fit and function of the prosthetic as measured by the ASDD-m. [ Time Frame: 4 weeks ]
   ASDD-m is a questionnaire for axillary hyperhidrosis measuring for presence, severity, impact and bothersomeness of the patient's sweating. There is a question that a patient rates from 0-10 (0 meaning no sweating at all, and 10 meaning worst possible sweating). Then there are two questions grated on a scale of 0-4 (0 meaning not at all and 4 meaning an extreme amount). So in total of 18 points with 0 meaning not bothered by swat at all, and 18 meaning that patients are extremely bothered by sweat.
2. Determine if patient's disease-related life quality is changed as a result of glycopyrronium cloth use as measured by the SKINDEX-16 [ Time Frame: 4 weeks ]
   Skindex-16 has 16 questions that accurately and sensitively measures how much patients are bothered by their skin conditions. We will determine the change in SKINDEX-16 scores between treatment and placebo periods. Skindex includes 16 questions that are rated on a scale from 0-6 (0 meaning never bothered by skin condition and 6 meaning always bothered by skin condition).

Secondary Outcome Measures :

1. Determining the change in the average weekly step count of weeks using the study treatment to weeks not using the study treatment. [ Time Frame: 12 weeks ]
   Patients will wear an activity monitor and we will compare their weekly average step count during the screening period to week 4 to the treatment period.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. History of limb amputation with limb-amputation surgery at least 6 months ago
2. Have a prosthetic device

4. HDSS of 3 or greater (at screening) 5. ASDD-m Item 2 severity score >= 4 (at screening) 6. PFFQ score >= 4 (at screening)

Exclusion Criteria:

1. Open sores or wounds on residual limb (at screening and baseline)
2. Known sensitivity to glycopyrronium tosylate or other component of Qbrexza
3. Pregnant or lactating.
4. Use of botulinum toxin within 1 year of the baseline visit
5. Use of topical aluminum chloride within 1 month of the baseline visit
6. Any significant concurrent condition that could adversely affect the patient's participation and/or the assessment of the safety and efficacy in the study in the opinion of the investigator

Contacts and Locations

Contacts

Contact: Adrianne Evans; 8012130375; adrianne.evans@hsc.utah.edu

Locations

United States, Utah

University of Utah MidValley Dermatology; Recruiting

Murray, Utah, United States, 84107

Contact: University of U Dermatology 801-213-0375 adrianne.evans@hsc.utah.edu

Principal Investigator: Stephanie Z Klein, MD

Sponsors and Collaborators

University of Utah

Investigators

• Principal Investigator: Stephanie Z Klein, MD; University of Utah

More Information

Publications:

Chren MM. The Skindex instruments to measure the effects of skin disease on quality of life. Dermatol Clin. 2012 Apr;30(2):231-6, xiii. doi: 10.1016/j.det.2011.11.003. Epub 2011 Dec 20. Review.

Hagberg K, Brånemark R. Consequences of non-vascular trans-femoral amputation: a survey of quality of life, prosthetic use and problems. Prosthet Orthot Int. 2001 Dec;25(3):186-94.

Hansen C, Godfrey B, Wixom J, McFadden M. Incidence, severity, and impact of hyperhidrosis in people with lower-limb amputation. J Rehabil Res Dev. 2015;52(1):31-40. doi: 10.1682/JRRD.2014.04.0108.

Strutton DR, Kowalski JW, Glaser DA, Stang PE. US prevalence of hyperhidrosis and impact on individuals with axillary hyperhidrosis: results from a national survey. J Am Acad Dermatol. 2004 Aug;51(2):241-8.

Nelson LM, DiBenedetti D, Pariser DM, Glaser DA, Hebert AA, Hofland H, Drew J, Ingolia D, Gillard KK, Fehnel S. Development and validation of the Axillary Sweating Daily Diary: a patient-reported outcome measure to assess axillary sweating severity. J Patient Rep Outcomes. 2019 Sep 5;3(1):59. doi: 10.1186/s41687-019-0148-8.

Lamb YN. Topical Glycopyrronium Tosylate in Primary Axillary Hyperhidrosis: A Profile of Its Use. Clin Drug Investig. 2019 Nov;39(11):1141-1147. doi: 10.1007/s40261-019-00853-x. Review. Erratum in: Clin Drug Investig. 2020 Jan;40(1):103.

Solish N, Bertucci V, Dansereau A, Hong HC, Lynde C, Lupin M, Smith KC, Storwick G; Canadian Hyperhidrosis Advisory Committee. A comprehensive approach to the recognition, diagnosis, and severity-based treatment of focal hyperhidrosis: recommendations of the Canadian Hyperhidrosis Advisory Committee. Dermatol Surg. 2007 Aug;33(8):908-23.

Ziegler-Graham K, MacKenzie EJ, Ephraim PL, Travison TG, Brookmeyer R. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil. 2008 Mar;89(3):422-9. doi: 10.1016/j.apmr.2007.11.005.

• Responsible Party: Stephanie Z Klein, Assistant Professor, Dermatology, Principal Investigator, University of Utah
• ClinicalTrials.gov Identifier: NCT04924036
• Other Study ID Numbers: IRB_00139912
• First Posted: June 11, 2021
• Last Update Posted: February 10, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Hyperhidrosis; Sweat Gland Diseases; Skin Diseases; Glycopyrrolate; Adjuvants, Anesthesia; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs