Clinical trial NCT01996995: Laser Therapy for Onychomycosis in Patients Wih Diabetes at Risk for Diabetic Foot Complications
Official title: Laser Therapy for Onychomycosis in Patients Wih Diabetes at Risk for Diabetic Foot Complications
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Onychomycosis
Lead sponsor: Medical Research Foundation, The Netherlands
Sponsor class: OTHER
First posted: 2013-11-27
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In a sham controlled double-blind trial we aim to establish the efficacy and safety of local application of laser therapy in patients with diabetes with onychomycosis and risk factors for diabetes related foot complications. Onychomycosis leads to thickened and distorted nails, which in turn leads to increased local pressure. The combination of onychomycosis and neuropathy or peripheral arterial disease (PAD) increases the risk of developing diabetes related foot complications. Usual care for high-risk patients with diabetes and onychomycosis is completely symptomatic with frequent skiving and clipping of the nails. No effective curative local therapies exist and systemic agents are often withheld due to concerns for side effects and interactions.

Aim: The primary aim is to evaluate the efficacy of 4 sessions N-YAG 1064nM laser application on the one-year clinical and microbiological cure rate in a randomised, double-blinded sham-controlled design with blinded outcome assessment.

Study population: Patients with diabetes mellitus, with an increased risk for diabetic foot ulcers.

Intervention: local laser treatment from a podiatrist and the other group receives treatment according to a control procedure. The laser procedure will be performed as a sham procedure by a second podiatrist.

Main study parameters/endpoints: The effect of 4 sessions of laser therapy on cure rate (clinical and microbiological) after one year.

Detailed description: Setting of the study: Hospital, outpatient departments (Foot clinic, Isala, Zwolle)

Inclusion criteria: Patients with clinical suspicion and microbiologic confirmation of onychomycosis , diagnosis of T1DM or T2DM, 18 years or older, at risk for diabetic foot ulcers defined by a modified Simm's classification score 1 or 2 with either neuropathy or PAD, nail involvement of at least 25% of the target nail.

Exclusion criteria: no microbiologic confirmation, Simms' classification score 3, the presence or history of diabetic foot ulcers, ischemic pain, ankle brachial index \< 0.9, patients receiving dialysis, severe renal insufficiently (eGFR below 30 ml/min), a documented toe pressure below 50 mmHg, use of systemic or topical antifungal agents 3 months prior to inclusion, use of immunosuppressive drugs, presence of psoriasis, lichen planus, or other abnormalities that could result in clinically abnormal toenails, a history of epilepsy and insufficient knowledge of the Dutch language. Patients with a dark skin color (Fitzpatrick 4 and 5) are excluded since dark skin color is associated with dark nails, which theoretically leads to increased temperatures during laser application

Eligibility criteria: Inclusion Criteria:

* Diabetes
* Over 18 years old
* Clinically suspicion with microbiologic confirmation of onychomycosis
* Patient is at risk for diabetic foot ulcers defines as Simms score 1, 2 .

Exclusion Criteria:

* Patients without the microbiological confirmation of fungal nail infection
* Patients with an active or history of a diabetic foot ulcer
* Patients who used systemic or topical anti fungal agents during the preceding 3 months
* Patients with ischemic rest pain
* Patients with ankle brachial index \< 0.9
* Patients with a documented toe pressure below 50 mmHg
* Patients receiving dialysis, severe renal insufficiently (eGFR below 30 ml/min)
* Patients with an insufficient knowledge of the Dutch language to understand requirements of the study
* Patients with a dark skin color (Fitspatrick 4 and 5)
* Patients who uses immunosuppressive medication
* Patient suffering from nail psoriasis , lichen planus, or other abnormalities that could result in clinically abnormal toenails.

Primary outcomes:
measure: complete cure of the target nail
timeFrame: outcome measured after 1 year
Secondary outcomes:
measure: Microbiological cure of the target nail
timeFrame: outcome measured after 1 year
measure: Complete clinical cure of the target nail
timeFrame: outcome measured after 1 year
measure: Markedly clinically improved target nail
timeFrame: outcome measured after 1 year
measure: Onychomycosis severity index below 6 (in patients with scores >6 at study entry) of the target nail
timeFrame: outcome measured after 1 year
measure: Complete clinical cure of all affected toes
timeFrame: outcome measured after 1 year
measure: Change in quality of life
timeFrame: outcome measured after 1 year
measure: Change surface healthy target nail / all clinically infected toes patients free of hyperkeratosis
timeFrame: outcome after 52 weeks
Other outcomes:
Locations:
city: Zwolle
country: Netherlands
facility: Isala Diabetes Centre, Isala Hospital
Study officials:
affiliation: Isala Diabetes Centre, Zwolle
name: H.J.G. Bilo, professor MD
role: STUDY_DIRECTOR
affiliation: Isala Diabetes Centre,Zwolle
name: Nanne Kleefstra, MD PhD
role: STUDY_DIRECTOR
affiliation: Isala Diabetes Centre, Zwolle
name: G.W.D. Landman, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Isala Diabetes Centre, Zwolle
name: Leonie Nijenhuis - Rosien, Bsc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nijenhuis-Rosien L, Kleefstra N, Wolfhagen MJ, Groenier KH, Bilo HJ, Landman GW. Laser therapy for onychomycosis in patients with diabetes at risk for foot complications: study protocol for a randomized, double-blind, controlled trial (LASER-1). Trials. 2015 Mar 22;16:108. doi: 10.1186/s13063-015-0622-4.