Clinical trial NCT05272969: Pompe & Pain - Study to Assess Nociceptive Pain in Adult Patients With Pompe Disease
Official title: Pompe & Pain - Observational Study to Assess Musculoskeletal Pain in Late-onset Pompe Disease (LOPD)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pompe Disease (Late-onset)
Inclusion Body Myositis
Spinal Muscular Atrophy Type 3
FSHD
Lead sponsor: LMU Klinikum
Sponsor class: OTHER
First posted: 2022-03-10
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: After screening of 120 patients, approximately 50 patients with late-onset Pompe disease, 15 patients with IBM, 15 patients with FSHD and 15 patients with SMA3, who meet all eligibility criteria, will be enrolled in the study. All patients must be ≥ 18 years of age.

Brief summary: The primary aim of this nationwide, explorative, cross-sectional study in Germany is to characterize the prevalence, severity and quality of musculoskeletal pain in adult patients with late-onset Pompe disease (LOPD). The secondary objectives are to evaluate whether muscle pain is associated with muscle function, to assess whether muscle pain is associated with alterations of muscle tissue, and whether vitamin D metabolism and polymorphisms of ACE and ACTN3 genes may contribute to an increased level of perceived musculoskeletal pain. In a second step, exome sequencing of genes associated with musculoskeletal pain will be analyzed. Results of LOPD patients will be compared to patients with neuromuscular disorders with a similar distribution of muscle weakness and/or musculoskeletal pain.

Detailed description: In this nationwide, explorative, cross-sectional study in Germany, approx. 50 patients with genetically confirmed late-onset Pompe disease (LOPD) will be included into the study. In addition, 15 Patients with histologically confirmed inclusion body myositis (IBM), 15 patients with genetically confirmed spinal muscular atrophy type 3 (SMA3) and 15 patients with genetically confirmed facio-scapulo-humeral muscle dystrophy (FSHD) will serve as a control group. The duration of patient recruitment will be around 18 months. The primary aim is to characterize the prevalence, severity and quality of musculoskeletal pain in adult patients with late-onset Pompe disease (LOPD). The secondary objectives are to evaluate whether muscle pain is associated with muscle function, measured by quantitative muscle testing and pressure pain threshold (PPT), to assess whether muscle pain is associated with alterations of muscle tissue, measured by muscle ultrasound and whether vitamin D metabolism and polymorphisms of ACE and ACTN3 genes may contribute to an increased level of perceived musculoskeletal pain. In a second step, exome sequencing of genes associated with musculoskeletal pain will be analyzed. Results of LOPD patients will be compared to patients with neuromuscular disorders with a similar distribution of muscle weakness and/or musculoskeletal pain.

After screening of 120 patients, approximately 50 patients with late-onset Pompe disease, 15 patients with IBM, 15 patients with FSHD and 15 patients with SMA3, who meet all eligibility criteria, will be enrolled in the study. All patients will be required to attend once at a study site to perform all study-related procedures. The study procedures will take approx. 3 hours.

Demographic and disease-related data (age, gender, weight, height, diagnosis, a historical genetic test results and/or muscle biopsy results, age at onset of symptoms, age at diagnosis, severity and distribution of muscle weakness, prior and concomitant medication, medical history, ventilation status) will be obtained. Patients will fill out validated disease-related and quality-of-life questionnaires: Brief Pain Inventory, Rotterdam Handicap Scale, Fatigue Severity Scale, R-PAct, and German Pain Questionnaire. Patients will be asked to sketch regions of perceived musculoskeletal pain on a body figure, which is provided on a tablet or a paper version. The paper version will be scanned and regions of muscular pain will be digitally evaluated to develop a map of musculoskeletal pain regions. For this, a novel software will be used, provided by the Institute for Information Engineering, Wolfenbüttel.

Muscle strength will be assessed clinically by MRC grading (0-5), by quick motor function test (QMFT) and by dynamometry of selected muscles.

Pressure Pain Threshold (PPT) is defined as the minimum force applied which induces pain. Pressure algometry measurements will be performed to assess PPTs on the trapezius, deltoid and supraspinatus muscles, the rectus femoris muscles, and the tibialis anterior muscles. For muscle function and endurance, a six-minute walk test will be performed. If this test was performed within the last 3 months (e.g. for routine treatment/assessments), no new test will be performed and the last assessment will be documented (distance walked in meters, borg scale, vital parameters and date of assessment). In muscle ultrasound, alterations of muscle tissue will be evaluated in selected muscles of proximal muscles of upper and lower limbs, cervical, thoracic and lumbar vertebral muscles and rectus abdominis muscle. In laboratory assessments, polymorphisms of ACE and ACTN3 will be analyzed by molecular analysis. Levels of creatine kinase (CK) and Vitamin D, calcium, phosphate and magnesium will be analyzed. In a second step upon additional informed consent, blood samples will be analyzed by exome sequencing for mutations and variants in common genes associated with chronic pain syndromes.

Eligibility criteria: Inclusion Criteria: A patient must meet the following criteria to be eligible for this study:

1. The patient is willing and able to provide signed informed consent.
2. The patient is able and willing to perform study-related assessments.
3. A) The patient is ≥18 years of age with acid α-glucosidase \[GAA\] enzyme deficiency, confirmed by GAA gene mutation analysis, or B) The patient has a histologically confirmed diagnosis of inclusion body myositis (IBM), or a genetically confirmed spinal muscular atrophy type 3 (SMA3) or a genetically confirmed facio-scapulo-humeral muscle dystrophy (FSHD).

Exclusion Criteria: A patient who meets any of the following criteria will be excluded from this study.

1. The patient is participating in another clinical study or using an investigational treatment.
2. The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study.
3. The patient has currently a severe depression, assessed by the Beck depression inventory fast screen (BDI-FS) with a score ≥ 4

Primary outcomes:
measure: Prevalence of musculoskeletal pain in LOPD patients
timeFrame: Only at baseline visit
Secondary outcomes:
measure: Association between musculoskeletal pain and muscle function, assessed by Medical research council (MRC) grading (0-5)
timeFrame: Only at baseline visit
measure: Association between musculoskeletal pain and muscle function, assessed by quick motor function test (QMFT)
timeFrame: Only at baseline visit
measure: Association between musculoskeletal pain and muscle function, assessed by Pressure Pain Threshold (PPT)
timeFrame: Only at baseline visit
measure: Association between musculoskeletal pain and alterations of muscles, assessed by muscle ultrasound
timeFrame: Only at baseline visit
measure: Association between musculoskeletal pain and Insertion-(I)-/Deletion-(D)-Polymorphisms of the ACE (angiotensin-converting enzyme; (ACE-I/D)) gene
timeFrame: Only at baseline visit
measure: Association between musculoskeletal pain and R-/X-polymorphisms of the Alpha-Actinin-3 (ACTN3) gene
timeFrame: Only at baseline visit
measure: Association between musculoskeletal pain and variants in defined genes, using exome sequencing
timeFrame: Only at baseline visit
measure: Characterization of musculoskeletal pain (quality and severity) assessed by the German Pain Questionnaire
timeFrame: Only at baseline visit
measure: Characterization of musculoskeletal pain (quality and severity) assessed by the Brief Pain Inventory (BPI)
timeFrame: Only at baseline visit
Other outcomes:
measure: Assessment of Questionnaire: Beck depression inventory fast screen
timeFrame: Only at baseline visit
measure: Assessment of Questionnaire: Rotterdam Handicap Scale (RHS)
timeFrame: Only at baseline visit
measure: Assessment of Questionnaire: R-Pact
timeFrame: Only at baseline visit
measure: Assessment of Questionnaire: Fatigue Severity and Disability Scale (FSS)
timeFrame: Only at baseline visit
Locations:
city: Munich
country: Germany
facility: Friedrich-Baur-Institute, Dep. of Neurology Klinikum der Universitaet Muenchen
state: Bavaria
Study officials:
affiliation: Study Principal Investigator
name: Stephan Wenninger, PD Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: