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)
1 other identifier
observational
95
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Mar 2022
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 28, 2022
CompletedFirst Posted
Study publicly available on registry
March 10, 2022
CompletedStudy Start
First participant enrolled
March 31, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 30, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
September 3, 2024
CompletedOctober 10, 2023
October 1, 2023
2.2 years
January 28, 2022
October 9, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Prevalence of musculoskeletal pain in LOPD patients
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).
Only at baseline visit
Secondary Outcomes (9)
Association between musculoskeletal pain and muscle function, assessed by Medical research council (MRC) grading (0-5)
Only at baseline visit
Association between musculoskeletal pain and muscle function, assessed by quick motor function test (QMFT)
Only at baseline visit
Association between musculoskeletal pain and muscle function, assessed by Pressure Pain Threshold (PPT)
Only at baseline visit
Association between musculoskeletal pain and alterations of muscles, assessed by muscle ultrasound
Only at baseline visit
Association between musculoskeletal pain and Insertion-(I)-/Deletion-(D)-Polymorphisms of the ACE (angiotensin-converting enzyme; (ACE-I/D)) gene
Only at baseline visit
- +4 more secondary outcomes
Other Outcomes (4)
Assessment of Questionnaire: Beck depression inventory fast screen
Only at baseline visit
Assessment of Questionnaire: Rotterdam Handicap Scale (RHS)
Only at baseline visit
Assessment of Questionnaire: R-Pact
Only at baseline visit
- +1 more other outcomes
Study Arms (2)
LOPD group
50 Patients with genetically confirmed late-onset Pompe disease.
Control group
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.
Interventions
Beck depression inventory fast screen questionnaire to detect severe depression for eligibility.
Validated questionnaire for pain.
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.
Validated questionnaire for perceived fatigue
validated questionnaire to assess a patient's functional ability and level of handicap
The R-PAct scale is designed specifically for Pompe disease, which consists of 18 items addressing daily life activities with three response options.
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.
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.
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.
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.
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.
Vital signs (blood pressure, heart rate, respiratory rate) will be measured before and after the six-Minute-Walk-Test (6MWT).
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).
CK-Level assessment in peripheral blood (peripheral venous blood draw)
Vitamin D Level in peripheral blood (peripheral venous blood draw)
calcium level in peripheral blood (peripheral venous blood draw)
magnesium level in peripheral blood (peripheral venous blood draw)
phosphate level in peripheral blood (peripheral venous blood draw)
peripheral venous blood draw for genetic analysis of ACE polymorphism
peripheral venous blood draw for genetic analysis of ACTN3 polymorphism
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".
Eligibility Criteria
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.
You may qualify if:
- The patient is willing and able to provide signed informed consent.
- The patient is able and willing to perform study-related assessments.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- LMU Klinikumlead
Study Sites (1)
Friedrich-Baur-Institute, Dep. of Neurology Klinikum der Universitaet Muenchen
Munich, Bavaria, 80336, Germany
Biospecimen
Polymorphisms of ACE and ACTN3. Upon additional informed consent, exome sequencing 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. 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".
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Stephan Wenninger, PD Dr. med.
Study Principal Investigator
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- CROSS SECTIONAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor of Neurology
Study Record Dates
First Submitted
January 28, 2022
First Posted
March 10, 2022
Study Start
March 31, 2022
Primary Completion
May 30, 2024
Study Completion
September 3, 2024
Last Updated
October 10, 2023
Record last verified: 2023-10
Data Sharing
- IPD Sharing
- Will not share