Metformin for the Treatment of Hidradenitis Suppurativa (HS)

Rediscovery of Metformin for the Chronic Disabling Auto-inflammatory Disease Hidradenitis Suppurativa

A randomized controlled trial investigating the metformin is the treatment for hidradenitis suppurativa. Metformin combined with doxycycline will be compared to the standard treatment of doxycycline monotherapy for HS severity and the effect on the pre-diabetic condition.

Study Overview

• Status: Completed
• Conditions: Hidradenitis Suppurativa
• Intervention / Treatment: Combination product: Metformin

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands
    • Erasmus MC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 years at baseline
• A diagnosis of HS for at least 1 year prior to baseline
• mild to moderately active disease defined by a HS Physician Global Assessment (HS-PGA) score of 2-3 and the Refined Hurley classification of mild to moderate at baseline
• Indication for systemic therapy; i.e. uncontrolled disease under conventional topical therapy.
• Able and willing to give written informed consent and to comply with the study requirements

Exclusion Criteria:

• Pregnant and lactating women
• Concomitant diabetes mellitus
• Use of antibiotics within 14 days prior to baseline
• Use of immunosuppressing/modulating therapies within 28 days prior to baseline
• A known allergy to metformin or doxycycline or any of the ingredients metformin or doxycycline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin combined with doxycycline	Combination product: Metformin; Metformin in combination with doxycycline
Placebo Comparator: Doxycyline combined with placebo	Combination product: Metformin; Metformin in combination with doxycycline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IHS4	International Hidradenitis Suppurativa Severity Score System (IHS4)	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin resistance	• Change in insulin resistance from baseline using the HOMA-IR (based on fasting glucose and insulin levels) and differences between the groups at week 12 and 24.	12 and 24 weeks
Lesion Count	• Change in lesion count from baseline and differences between the groups at 12 and 24 week. Difference in lesion count will be assessed between the groups at week 12 and 24.	12 and 24 weeks
NRS-Pain	Change in skin related pain from baseline, on a numerical rating scale, and differences between the groups at week 12 (V2) and 24 (V4)	12 and 24 weeks
Cost-effectiveness	• For cost-effectiveness the direct medical costs will be will be assessed using the iMTA Medical Consumption Questionnaire (iMCQ), The measurement will be at baseline, at 12 weeks and at 24 weeks. Productivity losses will be collected using the iMTA Productivity Cost Questionnaire (iPCQ) includes three modules measuring productivity losses of paid work due to 1) absenteeism and 2) presenteeism and productivity losses related to 3) unpaid work. The friction cost method for valuing the production losses will be applied in accordance to the Dutch manual for costing studies. Hence, the productivity loss will be valued per worker by age and gender and, for long term absences, taking into account that productivity costs to society is confined to the period needed to replace a worker (the friction period). Cost effectiveness will be estimated using Dutch manual for costing studies in economic evaluations (publication of the Health Care Institute (ZIN).	24 weeks
Bio-markers	The correlation between baseline calprotectin levels and disease severity for both groups.; The correlation between calprotectin levels and treatment response in each group at week 12 and 24.	24 weeks
Safety and Tolerability	• Incidence and severity of all adverse events (according to medDRA) will be analysed throughout the study, and renal function and lactate will be assessed at every visit.	up to 24 weeks
Metabolic syndrome	Change in parameters of metabolic syndrome (waist circumference, blood pressure, HDL cholesterol, and triglycerides) from baseline and differences between the groups at week 12 and 24.	12 and 24 weeks
Pre-diabetic disorder	Change in HbA1c from baseline and differences between the groups at week 12 and week 24.	12 and 24 weeks
HiSCR	The percentage of HiSCR achievers (a ≥ 50% reduction in inflammatory lesion count (abscesses + inflammatory nodules), and no increase in abscesses or draining fistulas when compared with baseline) and the difference between the groups at week 12 and 24.	12 and 24 weeks
HS-PGA	The change in HS-PGA from baseline and the difference between the groups at week 12 and 24.	12 and 24 weeks
Flares	Change in self-reported frequency of flares from baseline and differences between the groups at week 12 and 24.	12 and 24 weeks
DLQI	Change in quality of life from baseline and differences between the groups, measured with the Dermatologic Life Quality Index and the EQ-5D, at week 12 and 24.	12 and 24 weeks
Treatment satisfaction	Difference in treatment satisfaction and recommendation on a 5- and 3-point Likert scale respectively at week 12 and 24 between the groups.	up to 24 weeks

Collaborators and Investigators

• Sponsor: K.R. van Straalen

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2021
• Primary Completion (Actual): January 29, 2023
• Study Completion (Actual): August 23, 2023

Study Registration Dates

• First Submitted: November 16, 2020
• First Submitted That Met QC Criteria: November 24, 2020
• First Posted (Actual): December 2, 2020

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Sweat Gland Diseases; Skin Diseases; Infections; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Suppuration; Skin Diseases, Bacterial; Hidradenitis Suppurativa; Hidradenitis; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: EMCD20022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No