Pompe & Pain - Study to Assess Nociceptive Pain in Adult Patients With Pompe Disease
- Conditions
- Spinal Muscular Atrophy Type 3Inclusion Body MyositisFSHDPompe Disease (Late-onset)
- Interventions
- Diagnostic Test: Beck depression inventory fast screen (Questionnaire)Diagnostic Test: Brief Pain Inventory (BPI) (Questionnaire)Diagnostic Test: German Pain Inventory (Questionnaire)Diagnostic Test: Fatigue Severity and Disability Scale (FSS) (Questionnaire)Diagnostic Test: Rotterdam Handicap Scale (RHS) (Questionnaire)Diagnostic Test: R-PAct (Questionnaire)Diagnostic Test: Quick Motor Function TestDiagnostic Test: Handheld Dynamometry (HHD)Diagnostic Test: Six-minute walk test (6MWT)Diagnostic Test: Pressure pain thresholdDiagnostic Test: Muscle ultrasoundDiagnostic Test: Vital signsDiagnostic Test: Borg ScaleGenetic: Blood draw for optional genetic exome sequencing
- Registration Number
- NCT05272969
- Lead Sponsor
- LMU Klinikum
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 95
A patient must meet the following criteria to be eligible for this study:
- The patient is willing and able to provide signed informed consent.
- The patient is able and willing to perform study-related assessments.
- 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).
A patient who meets any of the following criteria will be excluded from this study.
- The patient is participating in another clinical study or using an investigational treatment.
- The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study.
- The patient has currently a severe depression, assessed by the Beck depression inventory fast screen (BDI-FS) with a score ≥ 4
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description LOPD group Beck depression inventory fast screen (Questionnaire) 50 Patients with genetically confirmed late-onset Pompe disease. LOPD group Brief Pain Inventory (BPI) (Questionnaire) 50 Patients with genetically confirmed late-onset Pompe disease. LOPD group R-PAct (Questionnaire) 50 Patients with genetically confirmed late-onset Pompe disease. LOPD group Fatigue Severity and Disability Scale (FSS) (Questionnaire) 50 Patients with genetically confirmed late-onset Pompe disease. LOPD group German Pain Inventory (Questionnaire) 50 Patients with genetically confirmed late-onset Pompe disease. LOPD group Rotterdam Handicap Scale (RHS) (Questionnaire) 50 Patients with genetically confirmed late-onset Pompe disease. LOPD group Quick Motor Function Test 50 Patients with genetically confirmed late-onset Pompe disease. LOPD group Handheld Dynamometry (HHD) 50 Patients with genetically confirmed late-onset Pompe disease. LOPD group Six-minute walk test (6MWT) 50 Patients with genetically confirmed late-onset Pompe disease. LOPD group Pressure pain threshold 50 Patients with genetically confirmed late-onset Pompe disease. LOPD group Muscle ultrasound 50 Patients with genetically confirmed late-onset Pompe disease. LOPD group Vital signs 50 Patients with genetically confirmed late-onset Pompe disease. LOPD group Borg Scale 50 Patients with genetically confirmed late-onset Pompe disease. LOPD group Blood draw for optional genetic exome sequencing 50 Patients with genetically confirmed late-onset Pompe disease. Control group Beck depression inventory fast screen (Questionnaire) 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. Control group Brief Pain Inventory (BPI) (Questionnaire) 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. Control group German Pain Inventory (Questionnaire) 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. Control group Fatigue Severity and Disability Scale (FSS) (Questionnaire) 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. Control group Rotterdam Handicap Scale (RHS) (Questionnaire) 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. Control group R-PAct (Questionnaire) 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. Control group Quick Motor Function Test 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. Control group Handheld Dynamometry (HHD) 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. Control group Six-minute walk test (6MWT) 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. Control group Pressure pain threshold 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. Control group Muscle ultrasound 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. Control group Vital signs 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. Control group Borg Scale 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. Control group Blood draw for optional genetic exome sequencing 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.
- Primary Outcome Measures
Name Time Method Prevalence of musculoskeletal pain in LOPD patients Only at baseline visit The primary aim of this nationwide, explorative, cross-sectional study in Germany is to characterize the prevalence of musculoskeletal pain in adult patients with late-onset Pompe disease (LOPD).
- Secondary Outcome Measures
Name Time Method Association between musculoskeletal pain and muscle function, assessed by quick motor function test (QMFT) Only at baseline visit Assessed by quick motor function test (QMFT). The QMFT is a clinical test. An evaluator assesses the performance of a patient and scores the items separately on a 5-point ordinal scale, ranging from 0 (not able) to 4 (normal performance). A total score is obtained by adding the scores of all items. The total score ranges between 0 and 64 points, a higher score means better performance.
Association between musculoskeletal pain and muscle function, assessed by Pressure Pain Threshold (PPT) Only at baseline visit Assessed by Pressure Pain Threshold (PPT). Pressure algometry is defined as the minimum force applied which induces pain. Measurements will be performed on the trapezius, deltoid and supraspinatus muscles, the rectus femoris muscles, and the tibialis anterior muscles. The assessor places the pressure algometer on a site to be inspected in 3 series of slowly increasing stimulus (contact area 1cm2) intensities (0.5 kg/s, corresponding to ca. 50 kPa/s). A higher score means a higher pressure pain threshold. There is no cutoff or total score.
Association between musculoskeletal pain and alterations of muscles, assessed by muscle ultrasound Only at baseline visit To assess whether musculoskeletal pain regions are associated with muscle tissue alteration, evaluated by muscle ultrasound, using the Heckmatt scale 1 (no alteration) to IV (dystrophic muscle). Lower scale means healthier muscle.
Characterization of musculoskeletal pain (quality and severity) assessed by the Brief Pain Inventory (BPI) Only at baseline visit To assess the severity of pain and the impact of pain on daily functions. The two categories Pain Intensity and Pain Interference are rated by patients on a scale from 0-10, 10 being excruciating pain intensity and a complete interference in their life. There is no scoring algorithm, but "worst pain" or the arithmetic mean of the four severity items can be used as measures of pain severity; the arithmetic mean of the seven interference items can be used as a measure of pain interference.
Association between musculoskeletal pain and muscle function, assessed by Medical research council (MRC) grading (0-5) Only at baseline visit Assessed by Medical research council (MRC) grading (0-5) of selected muscles: on both sides deltoid muscles, biceps brachii muscles, triceps brachii muscles, hip flexors, hip extensors, quadriceps femoris muscles, foot extensor and foot flexor muscles as well as axial muscles and neck flexors and extensors. A maximum score of 95 means no weakness, a minimum score of 0 means tetraplegia.
Association between musculoskeletal pain and R-/X-polymorphisms of the Alpha-Actinin-3 (ACTN3) gene Only at baseline visit ACTN3 genotyping (Alpha-Actinin-3 R-/X-polymorphisms) to assess whether R-/X-Polymorphisms of the ACTN3 gene are associated with musculoskeletal pain.
Association between musculoskeletal pain and Insertion-(I)-/Deletion-(D)-Polymorphisms of the ACE (angiotensin-converting enzyme; (ACE-I/D)) gene Only at baseline visit ACE genotyping (angiotensin-converting enzyme I/D polymorphisms) to assess whether Insertion-(I)-/Deletion-(D)-Polymorphisms of the ACE gene are associated with musculoskeletal pain.
Association between musculoskeletal pain and variants in defined genes, using exome sequencing Only at baseline visit to assess whether polymorphisms or pathogenic mutations in genes that are associated with chronic pain syndromes contribute to nociceptive pain, using exome sequencing of selected genes.
Characterization of musculoskeletal pain (quality and severity) assessed by the German Pain Questionnaire Only at baseline visit Characterization of quality and severity of musculoskeletal pain. The German Pain Questionnaire is a multidimensional questionnaire, based on several modules to characterize the quality of pain and consists of: demographic data, pain variables (e. g. pain sites, temporal characteristics, duration), pain associated symptoms, affective and sensory qualities of pain, pain-relieving and intensifying factors, previous pain treatment procedures, pain-related disability, comorbid conditions, social factors, and health-related quality of life. Module A, abbreviated questions of module S (sociodemographic questions S1, S2, S3, S4, S5 and S8) and module L (quality of life) and V (therapies) will be used. However, there is no total score that indicates e.g. lower or higher pain.
Trial Locations
- Locations (1)
Friedrich-Baur-Institute, Dep. of Neurology Klinikum der Universitaet Muenchen
🇩🇪Munich, Bavaria, Germany