Ignite Creation Date:
2024-05-06 @ 9:16 AM
Last Modification Date:
2024-10-26 @ 12:12 PM
Study NCT ID:
NCT02944799
Status:
COMPLETED
Last Update Posted:
2023-11-27
First Post:
2016-06-27
Brief Title:
Alendronate Treatment of Osteoporosis in Rheumatoid Arthritis
Sponsor:
University of Aarhus
Organization:
University of Aarhus
Study Overview
Official Title:
Alendronate Treatment of Osteoporosis in Rheumatoid Arthritis - Indication and Duration A Randomized Double-blind Placebocontrolled Study to Evaluate the Effects of Discontinuation of Alendronate in Patients With Both Rheumatoid Arthritis and Low Bone Mass
Status:
COMPLETED
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ALOSTRA
Brief Summary:
A randomized double-blind placebo-controlled trial including 160 consecutive patients who have been diagnosed with both rheumatoid arthritis RA and low bone mass and have been treated with alendronate ALN for five years or more Patients will be randomized to discontinuation or continuation of alendronate Outcomes are measured using dual energy absorptiometry DXA High Resolution peripheral Quantitative Computer Tomography HR-pQCT and biochemical markers of bone metabolism and inflammation after 6 months 1 and 2 years
Detailed Description:
Primary objectives
to assess the effect of discontinuation of alendronate ALN on C-terminal telopeptide crosslinks CTX and Type 1 procollagen amino-terminal-propeptide P1NP after 6 months
to assess the effect of discontinuation of ALN on bone mineral density BMD on DXA scans at 2 years
Secondary objectives
to assess the effect of discontinuation of ALN on vBMD on HRpQCT scans at 2 years
to assess the effect of discontinuation of ALN on biochemical markers of bone metabolism after 6 and 24 months
to evaluate and compare the changes in vBMD in cancellous and cortical bone respectively after discontinuation of ALN
to evaluate the correlation between RA activity measured by DAS28-CRP and bone metabolism
Interventions
Participants will be randomized to one of two groups
Group 1 Alendronate group N80 alendronate 70mgweekly calcium 800 mgday and vitamin D 38 µgday
Group 2 Placebo group N80 alendronate-placebo calcium 800 mgday and vitamin D 38 µgday
Concomitant treatment of RA
Patients included in this trial will be treated according to the national Danish guidelines for treatment of RA
Assignment of intervention
The Hospital Pharmacy in Aarhus will carry out the randomization Using the web-based programme randomizationcom a list of distribution is produced The randomization will be stratified according to which type of treatment the patients receives for RA All patients receiving traditional DMARDs such as methotrexate sulfasalazine hydroxychloroquine leflunomide or a combination hereof will be allocated to grop A All patients receiving any kind of biological treatment bDMARDs eg infliximab will be allocated to group B When requesting randomization from the hospital pharmacy the investigator will note if the patient is group A or B Both group A and B will undergo randomization 11 in the ALN and placebo groups using block randomization in blocks of 6
Participant timeline
Patients will be seen at a screening visit at baseline and after 3 6 12 and 24 months
Procedures at screening informed consent procedures full medical history full physical examination 12- lead EKG screening blood samples DXA scan
Procedures at all other visits focused physical exam of joints and back measurement of blood pressure pulse and temperature calculation of DAS28-CRP and HAQ scores screening for adverse events routine and project blood samples
At baseline visit HRpQCT scan and Xrays of hands and feet
At visit 12 months DXA and HRpQCT scans
At visit 24 months DXA and HRpQCT scans xrays of hands and feet
Clinical laboratory tests
routine analyses include alkaline phosphatase creatinine alanine aminotransferase ALT platelet count Hemoglobin white blood cells absolute neutrophil count absolute lymphocyte count CRP total 8ml
screening analyses routine analysis as well as s-FSH andor HCG women only calcium PTH vitamin-D status TSH total 16 ml
primary project analyses include CTX and P1NP total 4 ml
secondary project analysis include bone specific alkaline phosphatase RANK-L sclerostin tumor necrosis factor osteoprotegrin P1NP osteocalcin IL-6 IL-17 total 8 ml
extra blood bank sample - 3ml serum 2 ml plasma and full blood for storage and later analysis
DXA scan
Study participants will be scanned using a Hologic discovery machineTo ensure comparative results the same machine will be used for each participant at each scan Lumbar spine anterior-posterior and left hip pictures are recorded following local guidelines
HR-pQCT scan
Bone structure will be measured at metacarpals 2-4 and proximal radius using the model XTREME CT-I SCANCO MEDICAL AG SCHWEIZ A 27 cm long area over the right hand second and third metacarpophalangeal joint is scanned After this a 09 cm long part of the distal radius is scanned The 3D dataset will be analyzed and number and volume of erosions calculated Volumetric BMD is calculated for both cortical and trabecular bone trabecular number and separation according to the built-in software
X-rays of hands and feet
Standardized X-rays of the handsforearms and upper feet in separate AP dorsopalmar projections of each hand and wrist and dorsoplantar projections of the feet Images of the hands will be centered around the 2nd and 3rd MCPjoints The foot must not be tilted in the case of suboptimal projections of the MTP-joints All images will be scored centrally according to the Sharp-van der Heide score system
DAS28-CRP
A clinical activity score for arthritis activity is calculated by means of
number of tender and swollen joint scores including the following twenty eight joints shoulders elbows wrists metacarpophalangeal joints proximal interphalangeal joints and the knees
crp-measurement
general health assessment by the doctor using a VAS-scale A number between 0 and 10 is calculated Values 26 are considered in remission values 26 are considered as evidence of disease activity
Harms
The dose of radiation is estimated to 007mSievert as each HR-pQCT scan contributes with 0012mS each DXAscan 001mS and each Xray status of hands and feet 0008mS The average annual background radiation exposure in Denmark is 3mSievert Thus the participants will receive an increased radiation dose corresponding to 9 days of background radiation
The HR-pQCT-scans require fixation of the hand for 8 and 3 minutes respectively which might cause slight discomfort
Safety measures
All routine biochemical markers visit 1-5 will be analyzed and evaluated promptly An increase in alkaline phosphatase of more than 100 will lead to the participant being called in for an extra visit for further evaluation of the cause The patient will be withdrawn from the study if there is suspicion of accelerated bone loss
All fractures will be recorded and in the case of low-energy fracture the patient will be withdrawn from the study
The 12 month DXA scans will be reviewed and a BMD decrease of more than 5 will lead to exclusion from the study
to assess the effect of discontinuation of alendronate ALN on C-terminal telopeptide crosslinks CTX and Type 1 procollagen amino-terminal-propeptide P1NP after 6 months
to assess the effect of discontinuation of ALN on bone mineral density BMD on DXA scans at 2 years
Secondary objectives
to assess the effect of discontinuation of ALN on vBMD on HRpQCT scans at 2 years
to assess the effect of discontinuation of ALN on biochemical markers of bone metabolism after 6 and 24 months
to evaluate and compare the changes in vBMD in cancellous and cortical bone respectively after discontinuation of ALN
to evaluate the correlation between RA activity measured by DAS28-CRP and bone metabolism
Interventions
Participants will be randomized to one of two groups
Group 1 Alendronate group N80 alendronate 70mgweekly calcium 800 mgday and vitamin D 38 µgday
Group 2 Placebo group N80 alendronate-placebo calcium 800 mgday and vitamin D 38 µgday
Concomitant treatment of RA
Patients included in this trial will be treated according to the national Danish guidelines for treatment of RA
Assignment of intervention
The Hospital Pharmacy in Aarhus will carry out the randomization Using the web-based programme randomizationcom a list of distribution is produced The randomization will be stratified according to which type of treatment the patients receives for RA All patients receiving traditional DMARDs such as methotrexate sulfasalazine hydroxychloroquine leflunomide or a combination hereof will be allocated to grop A All patients receiving any kind of biological treatment bDMARDs eg infliximab will be allocated to group B When requesting randomization from the hospital pharmacy the investigator will note if the patient is group A or B Both group A and B will undergo randomization 11 in the ALN and placebo groups using block randomization in blocks of 6
Participant timeline
Patients will be seen at a screening visit at baseline and after 3 6 12 and 24 months
Procedures at screening informed consent procedures full medical history full physical examination 12- lead EKG screening blood samples DXA scan
Procedures at all other visits focused physical exam of joints and back measurement of blood pressure pulse and temperature calculation of DAS28-CRP and HAQ scores screening for adverse events routine and project blood samples
At baseline visit HRpQCT scan and Xrays of hands and feet
At visit 12 months DXA and HRpQCT scans
At visit 24 months DXA and HRpQCT scans xrays of hands and feet
Clinical laboratory tests
routine analyses include alkaline phosphatase creatinine alanine aminotransferase ALT platelet count Hemoglobin white blood cells absolute neutrophil count absolute lymphocyte count CRP total 8ml
screening analyses routine analysis as well as s-FSH andor HCG women only calcium PTH vitamin-D status TSH total 16 ml
primary project analyses include CTX and P1NP total 4 ml
secondary project analysis include bone specific alkaline phosphatase RANK-L sclerostin tumor necrosis factor osteoprotegrin P1NP osteocalcin IL-6 IL-17 total 8 ml
extra blood bank sample - 3ml serum 2 ml plasma and full blood for storage and later analysis
DXA scan
Study participants will be scanned using a Hologic discovery machineTo ensure comparative results the same machine will be used for each participant at each scan Lumbar spine anterior-posterior and left hip pictures are recorded following local guidelines
HR-pQCT scan
Bone structure will be measured at metacarpals 2-4 and proximal radius using the model XTREME CT-I SCANCO MEDICAL AG SCHWEIZ A 27 cm long area over the right hand second and third metacarpophalangeal joint is scanned After this a 09 cm long part of the distal radius is scanned The 3D dataset will be analyzed and number and volume of erosions calculated Volumetric BMD is calculated for both cortical and trabecular bone trabecular number and separation according to the built-in software
X-rays of hands and feet
Standardized X-rays of the handsforearms and upper feet in separate AP dorsopalmar projections of each hand and wrist and dorsoplantar projections of the feet Images of the hands will be centered around the 2nd and 3rd MCPjoints The foot must not be tilted in the case of suboptimal projections of the MTP-joints All images will be scored centrally according to the Sharp-van der Heide score system
DAS28-CRP
A clinical activity score for arthritis activity is calculated by means of
number of tender and swollen joint scores including the following twenty eight joints shoulders elbows wrists metacarpophalangeal joints proximal interphalangeal joints and the knees
crp-measurement
general health assessment by the doctor using a VAS-scale A number between 0 and 10 is calculated Values 26 are considered in remission values 26 are considered as evidence of disease activity
Harms
The dose of radiation is estimated to 007mSievert as each HR-pQCT scan contributes with 0012mS each DXAscan 001mS and each Xray status of hands and feet 0008mS The average annual background radiation exposure in Denmark is 3mSievert Thus the participants will receive an increased radiation dose corresponding to 9 days of background radiation
The HR-pQCT-scans require fixation of the hand for 8 and 3 minutes respectively which might cause slight discomfort
Safety measures
All routine biochemical markers visit 1-5 will be analyzed and evaluated promptly An increase in alkaline phosphatase of more than 100 will lead to the participant being called in for an extra visit for further evaluation of the cause The patient will be withdrawn from the study if there is suspicion of accelerated bone loss
All fractures will be recorded and in the case of low-energy fracture the patient will be withdrawn from the study
The 12 month DXA scans will be reviewed and a BMD decrease of more than 5 will lead to exclusion from the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None