The aim of this study is to determine the efficacy and durability of radiotherapy as treatment for patients with Ledderhose disease and to compare this to the natural course of Ledderhose disease.
ID
Source
Brief title
Condition
- Connective tissue disorders (excl congenital)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Numeric Rating Scale (NRS) score at 12 months:
The most important complaint of a patient with Ledderhose disease is pain,
generally irrespective of the size of the nodules. Therefore, the primary
endpoint will be pain relief at 12 months after treatment, measured by the
Numeric Rating Scale. This 11-point-scale is used to assess the worst pain
experienced by the patient in the previous week with scale endpoints from 0 (no
pain) to 10 (worst imaginable pain) points.
The pain response (complete or partial) is defined as a decrease of the initial
NRS-score by at least two points. Complete response is a NRS-score of 0 points.
A partial response is defined as a remaining NRS-score of at least 1 point.
Stable disease is defined as one or zero NRS-score point change in either
direction from the initial NRS-score. Progressive disease is defined as an
increase in the initial NRS-score of at least two points. Time to response and
time to progression are calculated from the date of randomisation until the
date of response and date of progression, respectively.
* A complete response (CR): NRS-score = 0.
* A partial response (PR): NRS-score = 1 and/or at least 2 points decrease from
initial NRS-score
* A stable disease (SD): 1-point NRS-score change from initial NRS-score in
either direction.
* A progressive disease (PD): Increase in at least 2 NRS-score points from the
initial NRS-score.
Secondary outcome
NRS-score at 6 and 18 months:
The NRS-score at 6 and 18 months will be scored the same way as NRS-score at 12
months.
Size of Ledderhose nodules at 12 months:
The size of the Ledderhose nodules will be measured using MRI and ultrasound at
12 months and compared with MRI and ultrasound at baseline.
10 meter straight line walk test
Patients will be asked at different time points to walk in a straight line for
10 meters at their usual (self-selected) speed and their maximum walking speed.
The VAS-score will be assessed before and after walking. Time points are
baseline, 6, 12 and 18 months.
PEDAR (UMCG only)
Pedobarography is a technique which can measure dynamic plantar foot pressure
during walking. Time points are baseline and 12 months.
Pain medication
The amount of pain medication will be scored at different time points. Time
points are baseline, 6, 12 and 18 months. The amount of pain medication
consumed in the week before each time point will be scored.
Questionnaires:
The RAND-36 and the brief pain inventory are questionnaires that will be filled
in at different time points. Time points are baseline, 6, 12 and 18 months, and
from 2 years annually until the end of follow-up.
* The RAND-36 item Health Survey (RAND-36): This is a short version of the RAND
Health Insurance Study Questionnaire and is almost identical to the Medical
Outcome Study (MOS) Short-Form-36 (SF-36). These questionnaires are used to
measure patient health.
* The brief pain inventory: This tool measures both the intensity of pain and
the interference of pain in the patient*s life.
* The EURO-QoL-5D: This is a standardised instrument to measure generic health
status.
Background summary
Ledderhose disease is a benign thickening of the plantar aponeurosis of the
foot. The disease appears as one or more subcutaneous painless nodules which
grow slowly. The nodules can become painful during walking, and are sometimes
disabling when they increase in size. Pain at rest does occur as cramps in the
affected foot and/or leg. The effect of conservative treatment with
physiotherapy, footpads and drugs is limited and can have the opposite effect.
When the symptoms become worse, a fasciectomy can be performed. However, this
surgical procedure is controversial because of the high risk of side effects
and limited durability. Radiotherapy has been proposed as an alternative
treatment. In studies investigating the effect of radiation on patients with
Ledderhose disease as primary treatment (see section existing evidence of
effectiveness), radiotherapy was effective in 60-88% and only minimal side
effects were seen. In a report of the Healthcare Insurance Board (CVZ), it was
concluded that the efficacy of radiotherapy for Ledderhose disease is unproven
as it has not been investigated in a randomised controlled trial (RCT).
Moreover, CVZ noticed that in one study that investigated postoperative
radiotherapy for Ledderhose disease, there were severe side effects and
long-term follow-up data missing. Therefore, it was advised that radiation
therapy for this indication should not be reimbursed. In contrast, based on the
same data as the CVZ report, the National Society of Radiotherapy and Oncology
(NVRO) stated that radiotherapy is a viable treatment option for patients with
Ledderhose disease. Furthermore, due to the high morbidity and recurrence rates
after surgery, patients only seldom receive surgery for Ledderhose disease in
The Netherlands anymore. Therefore, there is no effective treatment available
in The Netherlands that is covered by insurance companies. We plan to perform
an RCT to compare the effect of radiotherapy to the natural course of patients
with Ledderhose disease. The study will comprise adults with painful Ledderhose
disease who opt for radiotherapy after comprehensive consultation with a
plastic surgeon and a radiation oncologist.
Study objective
The aim of this study is to determine the efficacy and durability of
radiotherapy as treatment for patients with Ledderhose disease and to compare
this to the natural course of Ledderhose disease.
Study design
This study will be a multicentre, double blind RCT. To correct for placebo
effect or knowledge bias, we decided on a double-blind design.
* Arm 1: Sham-radiotherapy
* Arm 2: Radiotherapy
After randomisation, patients receive either sham-radiotherapy (arm 1) or
radiotherapy (arm 2). Patients assigned to the sham-radiotherapy arm will be
subjected to the same preparation procedures as patients assigned to the
radiotherapy arm. However, during sham treatment, patients will not receive
radiation, but only sounds of the treatment machine will be heard by the
patient. Neither the patient nor the treating radiation oncologist is aware of
the allocated treatment arm. The study will be unblinded for each patient at 18
months after treatment. Patients in the sham-radiotherapy (arm 1) will have the
opportunity to be treated with radiotherapy if complaints did not improve or
became worse.
Intervention
Radiotherapy:
After consultation of a plastic surgeon (who will confirm that the patient has
Ledderhose disease), patients will be referred to the radiotherapy department.
The patient will be first seen by a radiation oncologist who will explain the
study, the radiotherapy procedure and possible side effects. The possible side
effects are mild erythema of the skin, temporary increase of pain (about two
weeks) and very small chance (< 0.02% lifetime risk) of radiation induced
tumour. If the patients is willing to enter the study and has signed the
informed consent form, the patient will be randomised and the radiotherapy
procedure will be started. This procedure is identical in both treatment arms,
except that patients in treatment arm 1 (sham radiation) will not actually be
treated with radiation.
Patients will be positioned prone with their feet in a knee support. The
Ledderhose nodules will be marked and for the radiation field, margins will be
taken into account. Bolus material of 1 cm thickness will be placed over the
entire irradiated area. No specific OARs are defined. In general, all
recommended radiation protection measures will be applied especially to
minimize the risk of cancer from radiotherapy.
A custom lead (equivalent) mould of at least 10 mm thickness will be made for
each patient. Therefore, only the Ledderhose nodule and the skin directly
surrounding the nodule will be irradiated. The rest of the feet will be
shielded by this lead mould, in order to avoid unintended irradiation to the
rest of the body.
Radiotherapy will be performed using a linear accelerator with the capability
to radiate electrons. Radiotherapy will be administered in two separate
courses, each with five daily fractions of 3.0 Gy prescribed at each fraction.
The total dose will be 30 Gy. The interval between the two courses will be 10
weeks. Patients will be irradiated with 8-10 MeV electrons.
Study burden and risks
Burden:
* MRI, to measure the size of the Ledderhose nodules
* Ultrasound, to measure the size of the Ledderhose nodules
* 10 meter straight line walk test and PEDAR
* Patient-rated outcome measures (PROMs):
* MRS-score
* Pain medication
* Rand-36 item Health Survey
* The brief pain inventory
* EURO-QoL-5D
Risks:
Patients randomized to placebo arm will first not receive any treatment.
Very low chance on developing radiation induced malignancy (estimated risk:
0.02% long life)
Justification:
With this study the effectiveness of Radiotherapy as a treatment option for
Ledderhose Disease can be proven.
Every patient randomized for placebo arm will get the opportunity to be treated
with Radiotherapy after 18 months.
The chance on developing radiation induced malignany is neglectable.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
• Patients with painful Ledderhose disease. The pain score measured with the
VAS score and is at least 2 on the 11-point scale (0 = no pain to 10 = worst
imaginable pain).
• Age >= 18 years
• WHO performance status 0, 1 or 2
• Before patient randomisation, written informed consent must be given
according to ICH/GCP, and local regulations
• Able and willing to complete quality of life questionnaires in English or
Dutch
• Must be accessible for treatment follow-up
Exclusion criteria
• Surgical intervention before for Ledderhose disease
• Previous radiation treatment for Ledderhose disease
• Any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule
• Not able to lay prone for at least fifteen minutes
• Females who are pregnant at entry or who want to become pregnant within six
months.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL62429.042.17 |
| Other | volgt |