NCT05272969

Pompe & Pain - Study to Assess Nociceptive Pain in Adult Patients With Pompe Disease

Pompe & Pain - Observational Study to Assess Musculoskeletal Pain in Late-onset Pompe Disease (LOPD)

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 95 (estimated)
• Sponsor: LMU Klinikum · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Pompe Disease (Late-onset)
• Inclusion Body Myositis
• Spinal Muscular Atrophy Type 3
• FSHD

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Beck depression inventory fast screen (Questionnaire)	Beck depression inventory fast screen questionnaire to detect severe depression for eligibility.
DIAGNOSTIC_TEST	Brief Pain Inventory (BPI) (Questionnaire)	Validated questionnaire for pain.
DIAGNOSTIC_TEST	German Pain Inventory (Questionnaire)	German Pain Inventory questionnaire for evaluation of pain. 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.
DIAGNOSTIC_TEST	Fatigue Severity and Disability Scale (FSS) (Questionnaire)	Validated questionnaire for perceived fatigue
DIAGNOSTIC_TEST	Rotterdam Handicap Scale (RHS) (Questionnaire)	validated questionnaire to assess a patient's functional ability and level of handicap
DIAGNOSTIC_TEST	R-PAct (Questionnaire)	The R-PAct scale is designed specifically for Pompe disease, which consists of 18 items addressing daily life activities with three response options.
DIAGNOSTIC_TEST	Quick Motor Function Test	An evaluator observes the performance of a patient and scores the items separately on a 5-point ordinal scale (ranging from 0 to 4). A total score is obtained by adding the scores of all items and ranges between 0 and 64 points.
DIAGNOSTIC_TEST	Handheld Dynamometry (HHD)	To ensure a high level of objective measurement, muscle strength will also be assessed by handheld dynamometry. The following muscle groups will be tested: Arm abduction, elbow flexion, elbow extension, hip flexion, hip extension, knee extension, knee flexion, foot extension, foot flexion.
DIAGNOSTIC_TEST	Six-minute walk test (6MWT)	It is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. If a six-minute-walk-test was performed within the last 3 months within the routine treatment, no additional test will be performed and the distance walked in meters as well as borg scale will be recorded in the study CRF, including the date of the assessment. If not performed within the last six months, a six-minute-walk test will be performed once.
DIAGNOSTIC_TEST	Pressure pain threshold	For diagnosis of myofascial pain, pressure algometers are designed and conventionally used to measure deep pressure pain thresholds or tenderness resistance (Park, Kim et al. 2011), and the reliability of pressure pain thresholds according to raters or measurement frequencies has been proven to be relatively high (Chung, Um et al. 1992). The threshold is then determined as the arithmetic mean of the 3 series (in kPa). The measurement will be stopped immediately as the patient feels sensations of "burning", "stinging", "drilling" or "aching. Pressure algometry measurements will be performed on the trapezius, deltoid and supraspinatus muscles, the rectus femoris muscles, and the tibialis anterior muscles.
DIAGNOSTIC_TEST	Muscle ultrasound	Muscle ultrasound is an ideal imaging modality that allows for atraumatic, noninvasive, radiation-free point-of-care neuromuscular imaging. Muscular diseases are typically associated with an increase in the echogenicity from the muscle substance, distal attenuation of muscle echo and a corresponding loss of bone echo. A measurement on both sides deltoid, biceps and triceps brachii muscle, quadriceps femoris muscle, tibialis anterior muscle, rectus abdominis muscle and paravertebral muscles of cervical (C5-7), thoracic (Th4-6) and lumbar (L4-5) muscles. Muscle tissue alterations will be classified using the Heckmatt scale I-IV, describing muscle echogenicity. For muscle ultrasound, a linear 17MHz probe will be used. The muscle ultrasound assessment usually takes 15-20 minutes.
DIAGNOSTIC_TEST	Vital signs	Vital signs (blood pressure, heart rate, respiratory rate) will be measured before and after the six-Minute-Walk-Test (6MWT).
DIAGNOSTIC_TEST	Borg Scale	The Borg scale will be assessed, which is a self-reported questionnaire designed to subjectively assess dyspnea and exertion during activity (Borg 1982). The Borg scale rates dyspnea on a scale of 0 to 10 incorporating nonlinear spacing of verbal descriptors of the level of intensity of dyspnea. A higher Borg score indicates more severe dyspnea. The Borg scale will be administered before starting the 6MWT (≤ 5 minutes) and after completing the 6MWT (≤ 5 minutes).
DIAGNOSTIC_TEST	Laboratory assessment: Creatine kinase	CK-Level assessment in peripheral blood (peripheral venous blood draw)
DIAGNOSTIC_TEST	Laboratory assessment: Vitamin D Level	Vitamin D Level in peripheral blood (peripheral venous blood draw)
DIAGNOSTIC_TEST	Laboratory assessment: calcium	calcium level in peripheral blood (peripheral venous blood draw)
DIAGNOSTIC_TEST	Laboratory assessment: magnesium	magnesium level in peripheral blood (peripheral venous blood draw)
DIAGNOSTIC_TEST	Laboratory assessment: phosphate	phosphate level in peripheral blood (peripheral venous blood draw)
GENETIC	Genetic test: ACE polymorphism	peripheral venous blood draw for genetic analysis of ACE polymorphism
GENETIC	Genetic test: ACTN3 polymorphism	peripheral venous blood draw for genetic analysis of ACTN3 polymorphism
GENETIC	Blood draw for optional genetic exome sequencing	Optionally, upon additional informed consent, exome sequencing from peripheral blood will be performed in a second step to assess whether polymorphisms or pathogenic mutations in genes that are associated with chronic pain syndromes contribute to increased pain. This analysis will be performed collectively after enrollment is complete by the Genetikum Neu-Ulm. The selection of the genes is based on the Human Phenotype Ontology (HPO) search terms "myalgia", "muscle pain", "chronic pain", "musculoskeletal pain", "pain", and "nociceptive pain".

Timeline

• Start date: 2022-03-31
• Primary completion: 2024-05-30
• Completion: 2024-09-03
• First posted: 2022-03-10
• Last updated: 2023-10-10

Locations

1 site across 1 country: Germany