Metformin for the Treatment of Hidradenitis Suppurativa (HS)
Primary Purpose
Hidradenitis Suppurativa
Status
Completed
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
Metformin
Sponsored by
About this trial
This is an interventional treatment trial for Hidradenitis Suppurativa
Eligibility 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
Sites / Locations
- Erasmus MC
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Metformin combined with doxycycline
Doxycyline combined with placebo
Arm Description
Outcomes
Primary Outcome Measures
IHS4
International Hidradenitis Suppurativa Severity Score System (IHS4)
Secondary Outcome Measures
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.
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.
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)
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).
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.
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.
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.
Pre-diabetic disorder
Change in HbA1c from baseline and differences between the groups at week 12 and week 24.
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.
HS-PGA
The change in HS-PGA from baseline and the difference between the groups at week 12 and 24.
Flares
Change in self-reported frequency of flares from baseline and differences between the groups at week 12 and 24.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04649502
Brief Title
Metformin for the Treatment of Hidradenitis Suppurativa (HS)
Official Title
Rediscovery of Metformin for the Chronic Disabling Auto-inflammatory Disease Hidradenitis Suppurativa
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
January 25, 2021 (Actual)
Primary Completion Date
January 29, 2023 (Actual)
Study Completion Date
August 23, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
K.R. van Straalen
4. Oversight
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
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hidradenitis Suppurativa
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
randomized controlled trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double blind
Allocation
Randomized
Enrollment
62 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Metformin combined with doxycycline
Arm Type
Experimental
Arm Title
Doxycyline combined with placebo
Arm Type
Placebo Comparator
Intervention Type
Combination Product
Intervention Name(s)
Metformin
Intervention Description
Metformin in combination with doxycycline
Primary Outcome Measure Information:
Title
IHS4
Description
International Hidradenitis Suppurativa Severity Score System (IHS4)
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Insulin resistance
Description
• 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.
Time Frame
12 and 24 weeks
Title
Lesion Count
Description
• 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.
Time Frame
12 and 24 weeks
Title
NRS-Pain
Description
Change in skin related pain from baseline, on a numerical rating scale, and differences between the groups at week 12 (V2) and 24 (V4)
Time Frame
12 and 24 weeks
Title
Cost-effectiveness
Description
• 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).
Time Frame
24 weeks
Title
Bio-markers
Description
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.
Time Frame
24 weeks
Title
Safety and Tolerability
Description
• 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.
Time Frame
up to 24 weeks
Title
Metabolic syndrome
Description
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.
Time Frame
12 and 24 weeks
Title
Pre-diabetic disorder
Description
Change in HbA1c from baseline and differences between the groups at week 12 and week 24.
Time Frame
12 and 24 weeks
Title
HiSCR
Description
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.
Time Frame
12 and 24 weeks
Title
HS-PGA
Description
The change in HS-PGA from baseline and the difference between the groups at week 12 and 24.
Time Frame
12 and 24 weeks
Title
Flares
Description
Change in self-reported frequency of flares from baseline and differences between the groups at week 12 and 24.
Time Frame
12 and 24 weeks
Title
DLQI
Description
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.
Time Frame
12 and 24 weeks
Title
Treatment satisfaction
Description
Difference in treatment satisfaction and recommendation on a 5- and 3-point Likert scale respectively at week 12 and 24 between the groups.
Time Frame
up to 24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Erasmus MC
City
Rotterdam
Country
Netherlands
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Metformin for the Treatment of Hidradenitis Suppurativa (HS)
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