PAmidronate for Pain in Sternocostoclavicular hyperostosis: the PAPS-study, a double-blind randomized placebo-controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Academisch Ziekenhuis Leiden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

8 Dec 2020 → ongoing

Decision date (initial)

2024-08-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Reuma Nederland

External identifiers

EU CT number

2023-510309-16-00

EudraCT number

2020-001068-27

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To demonstrate that in CNO patients with pain 3-monthly treatment with pamidronate will result in a significant decrease in maximal pain score (as measured by Brief Pain Inventory (BPI) (10), compared to placebo.

Secondary objectives 14

1. To study the number of patients with mild pain (4 on BPI or below) after 3-monthly treatment with pamidronate
2. To study the number of patients with 50% reduction in maximal pain (NRS score in BPI)
3. To study change in shoulder rating questionnaire (SRQ) (11) and facets of Shoulder function assessment (SFA) (12) score (among which is ability to dress)
4. To study change in range of motion
5. To study improvement in general health as measured with Short Form Health Survey (Sf-36) (13), work activity score (14) , and physical activity International Physical Activity Questionnaire (IPAQ, short form, previous 7 days) (15)
6. To investigate partner burden before and after therapy using Care-related Quality of Life Instrument (CarerQol) (16)
7. To study a change in standard dose of analgesics during course of the study as evidence for efficacy of treatment
8. Evaluation of confounding factors for outcome of treatment such as delay in diagnosis and the amount of baseline tracer uptake, pain and range of motion
9. Significant alteration of inflammation and quantifiable decrease in Na18F-PET/CT tracer uptake of CNO lesions after pamidronate therapy, and its relation to disease symptoms as measured using above mentioned questionnaires and SFA
10. Evaluation of a possible neuropathic component of the reported pain (Pain Detect)
11. To estimate the number of CNO patients exhibiting signs of central pain sensitization by Central Sensitization Inventory (CSI) (18)
12. To determine the association between central sensitization symptomatology and patient reported outcomes (pain) after treatment with pamidronate/placebo, amongst which the primary outcome measure (maximal pain)
13. To assess spinal involvement of CNO-lesions
14. To evaluate cost-effectiveness of therapy in an economic evaluation

Conditions and MedDRA coding

Inflammation of sternal region

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. NRS score for maximal pain of ≥ 6/10 at lesion sites
2. Signs of disease activity on imaging at lesion sites
3. No treatment with bisphosphonates for the previous 6 months

Exclusion criteria 10

1. Age below 18 years of age
2. Active pregnancy wish, pregnancy or nursing
3. Generalized pain without CNO related pain
4. Bisphosphonate allergy
5. Estimated glomerular filtration rate < 30 ml/min
6. Uncontrolled endocrine abnormalities
7. Active cancer treatment
8. Language barrier
9. Severe co-morbidity, including poor mobility and other causes preventing attendance for control visits
10. Mental disability

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in score of maximal pain on BPI (NRS 0-10) from baseline to 6 months

Secondary endpoints 14

1. Change in range of motion
2. Number of patients with mild pain (maximal pain as measured with NRS score in BPI ≤4)
3. Number of patients with 50% reduction in maximal pain (NRS score in BPI)
4. Change in shoulder rating questionnaire and facets of SFA score (among which are ability to dress)
5. Change in general health, quality of life, fatigue, work activity score, physical activity, and partner burden
6. Change in standard dose of analgesics (including NSAIDs) possible during course of the study as evidence for efficacy of treatment
7. Evaluation of confounding factors for outcome of treatment such as delay in diagnosis and the amount of baseline tracer uptake, pain and range of motion
8. Evaluation of a possible neuropathic component of the reported pain
9. Number of CNO patients exhibiting signs of central sensitization
10. Association between central sensitization and therapeutic response
11. Change in biochemical markers of inflammation
12. Amount of tracer uptake of CNO lesions on Na18F-PET/CT
13. Spinal involvement
14. Cost-effectiveness

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Academisch Ziekenhuis Leiden

Sponsor organisation

Academisch Ziekenhuis Leiden

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

E.M. Winter

Public contact point

Organisation

Academisch Ziekenhuis Leiden

Contact name

E.M. Winter

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications