Metformin for the Treatment of Hidradenitis Suppurativa (HS)

• ClinicalTrials.gov Identifier: NCT04649502
• Recruitment Status: Not yet recruiting
• First Posted: December 2, 2020
• Last Update Posted: December 2, 2020
• Sponsor: K.R. van Straalen
• Information provided by (Responsible Party): K.R. van Straalen, Erasmus Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hidradenitis Suppurativa	Combination Product: Metformin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 62 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: randomized controlled trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double blind
• Primary Purpose: Treatment
• Official Title: Rediscovery of Metformin for the Chronic Disabling Auto-inflammatory Disease Hidradenitis Suppurativa
• Estimated Study Start Date: January 25, 2021
• Estimated Primary Completion Date: January 29, 2023
• Estimated Study Completion Date: January 29, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. IHS4 [ Time Frame: 24 weeks ]
   International Hidradenitis Suppurativa Severity Score System (IHS4)

Secondary Outcome Measures :

1. Insulin resistance [ Time Frame: 12 and 24 weeks ]
   • 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.
2. Lesion Count [ Time Frame: 12 and 24 weeks ]
   • 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.
3. NRS-Pain [ Time Frame: 12 and 24 weeks ]
   Change in skin related pain from baseline, on a numerical rating scale, and differences between the groups at week 12 (V2) and 24 (V4)
4. Cost-effectiveness [ Time Frame: 24 weeks ]
   • 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).
5. Bio-markers [ Time Frame: 24 weeks ]
   • 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.
6. Safety and Tolerability [ Time Frame: up to 24 weeks ]
   • 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.
7. Metabolic syndrome [ Time Frame: 12 and 24 weeks ]
   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.
8. Pre-diabetic disorder [ Time Frame: 12 and 24 weeks ]
   Change in HbA1c from baseline and differences between the groups at week 12 and week 24.
9. HiSCR [ Time Frame: 12 and 24 weeks ]
   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.
10. HS-PGA [ Time Frame: 12 and 24 weeks ]
    The change in HS-PGA from baseline and the difference between the groups at week 12 and 24.
11. Flares [ Time Frame: 12 and 24 weeks ]
    Change in self-reported frequency of flares from baseline and differences between the groups at week 12 and 24.
12. DLQI [ Time Frame: 12 and 24 weeks ]
    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.
13. Treatment satisfaction [ Time Frame: up to 24 weeks ]
    Difference in treatment satisfaction and recommendation on a 5- and 3-point Likert scale respectively at week 12 and 24 between the groups.

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:

• 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

Contacts and Locations

Contacts

Contact: Kelsey van Straalen, MD; +31 10 704 0110; k.vanstraalen@erasmusmc.nl

Sponsors and Collaborators

K.R. van Straalen

More Information

• Responsible Party: K.R. van Straalen, MD., Erasmus Medical Center
• ClinicalTrials.gov Identifier: NCT04649502
• Other Study ID Numbers: EMCD20022
• First Posted: December 2, 2020
• Last Update Posted: December 2, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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

Additional relevant MeSH terms:

Hidradenitis Suppurativa; Hidradenitis; Sweat Gland Diseases; Skin Diseases; Skin Diseases, Bacterial; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Skin Diseases, Infectious; Suppuration; Metformin; Hypoglycemic Agents; Physiological Effects of Drugs