Bone DemineralizationPhase 4APARTNCT02322099
Alendronate for Prevention of AntiRetroviral Therapy-associated Bone Loss
A Phase 4 study testing Alendronate, calcium carbonate and colecalciferol and Tenofovir disoproxil in people with Bone Demineralization, run by University College Dublin at 2 sites in Ireland.
Trial summary
Antiretroviral therapy (ART) initiation is associated with a significant loss of bone mineral density (BMD), characterised by increases in bone turnover, which is largely limited to the first 48 weeks of therapy. Bisphosphonates, such as alendronate, decrease bone turnover and can limit loss of bone mineral density. Read more about this study
- Who is it for?
- Ages 30 years and older
- Conditions the study is for
- Bone Demineralization
- What is being tested?
- Alendronate, calcium carbonate and colecalciferol and Tenofovir disoproxil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 2 sitesIreland
- Study dates
- May 2016to Sep 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- male>30 years old or female>35 years old
- HIV-1 antibody positive
- antiretroviral therapy naïve
- be presumed to have achieved peak bone mass
- be eligible for initiation of antiretroviral therapy in the opinion of the investigator
- be able to provide written, informed consent
Who cannot join
- subjects unable to comply with the study protocol or unable to stand/sit upright for at least 30 minutes
- history of osteoporosis
- history of fragility fracture or previous femoral fracture
- chronic renal failure
- hypocalcemia or hypercalcemia at screening
- history of Paget's disease or known primary hyperparathyroidism
Show all 17Show fewer
- previous treatment with or allergy (including hypersensitivity) to bisphosphonates
- recent history (past 12 months) of peptic or duodenal ulcers or oesophagitis, aspiration or any other abnormality of the oesophagus
- current therapy with prescribed calcium or vitamin D preparations (other than over-the-counter multivitamin preparations)
- current therapy with aspirin or other regularly prescribed non-steroidal anti-inflammatory drugs
- recent dental work (within the past 3 months) or poor oral hygiene (as judged in the opinion of the investigator)
- recent (within the past three months) significant steroid exposure
- for female subjects: pregnancy at screening, planning future pregnancies or unwilling to take measures to avoid pregnancy for the duration of the study
- where in the investigator's opinion, there is a necessity to initiate ART within the pre-ART study window period
- hepatitis B or hepatitis C co-infection
- any active illness (including AIDS illness) which in the opinion of the investigator precludes participation in the study
- subjects concurrently enrolled in another clinical trial of an investigational medical product
Trial locations and contacts
2 sites in 1 country.
Ireland2 sites
Mater Misericordiae University Hospital
Dublin, 7
Beaumont Hospital
Dublin, 9
About this study
Official title: A Multi-centre, Prospective, Randomised Trial of Short Course Alendronate Therapy or Placebo Combined With Vitamin D and Calcium to Prevent Loss of Bone Mineral Density in Antiretroviral-naïve, HIV-1 Infected Subjects Initiating Antiretroviral Therapy
Antiretroviral therapy (ART) initiation is associated with a significant loss of bone mineral density (BMD), characterised by increases in bone turnover, which is largely limited to the first 48 weeks of therapy. Bisphosphonates, such as alendronate, decrease bone turnover and can limit loss of bone mineral density.
This study aims to determine if a short course of treatment with the oral bisphosphonate alendronate can limit loss of bone mineral density associated with initiation of ART in HIV-1 infected, antiretroviral naive, adult subjects.
Read the detailed description
Multi-centre, prospective, randomised, double-blind, placebo-controlled trial over 50 weeks. The aims of this study include:
- To determine if short-course treatment with alendronate versus placebo combined with calcium and vitamin D, initiated 2 weeks prior to start of ART and can prevent loss of BMD over 48 weeks of follow-up post ART initiation.
- To explore the effect of alendronate on bone turnover in the setting of ART initiation.
- To determine which factors, such as choice of ART, impacts the protective effect of alendronate in preventing BMD loss.
- To determine the relationship between changes in bone turnover markers, vitamin D, parathyroid hormone and calcium levels.
- To explore the pathogenesis of BMD loss with initiation of ART by investigating relationships between changes in immune function (T-cells and B-cells subsets), bone turnover and BMD.
- Conditions
- Bone Demineralization
- Being tested
- Alendronate, Placebo, calcium carbonate and colecalciferol, Tenofovir disoproxil
- Keywords
- human immunodeficiency virus, bone diseases, osteopenia, osteoporosis, fracture, bone turnover, alendronate, antiretroviral
- Medical subject headings
- Bone Demineralization, Pathologic, Acquired Immunodeficiency Syndrome, Bone Diseases, Bone Diseases, Metabolic, Osteoporosis, Fractures, Bone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlendronateDrug
Also called Fosamax, Romax
alendronate 70 mg tablets to be administered weekly for a total of 14 weeks, commencing 2 weeks prior to ART initiation
PlaceboDrug
Sugar pill manufactured to mimic alendronate 70 mg tablet administered weekly for a total of 14 weeks, commencing 2 weeks prior to ART
calcium carbonate and colecalciferolDietary supplement
Also called Calcichew D3 forte, Ideos
Calcium carbonate 1250 mg (equivalent to 500 mg of elemental calcium) and colecalciferol 400 iu (equivalent to 10 micrograms of vitamin D3) tablets administered twice daily for a total of 14 weeks, commencing 2 weeks prior to ART initiation
Tenofovir disoproxilDrug
Also called Truvada
Emtricitabine / tenofovir disoproxil fumarate 200 / 300 mg tablet administered once-daily with food (open-label) commencing 2 weeks after alendronate initiation and continuing for 48 weeks
| Study group | Role | What they receive |
|---|---|---|
| Alendronate | Active comparator | Alendronate 70 mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada® Receives: Drug: Alendronate; Dietary Supplement: calcium carbonate and colecalciferol; Drug: Tenofovir disoproxil |
| Placebo | Placebo comparator | Placebo to alendronate 70mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada® Receives: Drug: Placebo; Dietary Supplement: calcium carbonate and colecalciferol; Drug: Tenofovir disoproxil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of changes in bone mineral density
Between-group differences in percentage change in total hip, lumbar spine, femoral neck BMD and body composition to week 50 among subjects who received at least one dose of the study medication
Measured: 50 weeks
Secondary outcomes (2)
Rate of changes in bone turnover markers
Between-group differences in percentage change in bone turnover markers
Measured: 50 weeks
Impact of ART choice on alendronate protective effect
Impact of choice of ART on changes in BMD and bone turnover markers
Measured: 50 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2014 (estimated)
- Study startMay 2016
- Primary completionSep 2019
- Study completionSep 2019
Why it stopped: Due to the COVID-19 pandemic the study was terminated prematurely
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Bone DemineralizationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College Dublin
- Sponsor type
- University, hospital or other
- Collaborators
- Health Research Board, Ireland, Royal College of Surgeons, Ireland, Mater Misericordiae University Hospital, Beaumont Hospital, Rush University Medical Center
- Responsible party
- Principal investigator, Patrick Mallon, University College Dublin
- Investigators
- Patrick WG Mallon, MB BCh BAO,PhD,FRCPI, Principal investigator, University College Dublin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02322099
- Sponsor's protocol ID
- APART_2014
- Acronym
- APART
- Status last verified
- May 2022
- First submitted
- 17 Dec 2014
- Last updated
- 26 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Cotter AG, Sabin CA, Simelane S, Macken A, Kavanagh E, Brady JJ, McCarthy G, Compston J, Mallon PW; HIV UPBEAT Study Group. Relative contribution of HIV infection, demographics and body mass index to bone mineral density. AIDS. 2014 Sep 10;28(14):2051-60. doi: 10.1097/QAD.0000000000000353.
PubMed 25265073McComsey GA, Kendall MA, Tebas P, Swindells S, Hogg E, Alston-Smith B, Suckow C, Gopalakrishnan G, Benson C, Wohl DA. Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV. AIDS. 2007 Nov 30;21(18):2473-82. doi: 10.1097/QAD.0b013e3282ef961d.
PubMed 18025884
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-centre, Prospective, Randomised Trial of Short Course Alendronate Therapy or Placebo Combined With Vitamin D and Calcium to Prevent Loss of Bone Mineral Density in Antiretroviral-naïve, HIV-1 Infected Subjects Initiating Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT02322099
- Acronym / sponsor ID
- APART / APART_2014
- Conditions
- Bone Demineralization
- Keywords
- human immunodeficiency virus, bone diseases, osteopenia, osteoporosis, fracture, bone turnover, alendronate, antiretroviral
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to the COVID-19 pandemic the study was terminated prematurely
- Enrolment
- 53 participants (actual)
- Lead sponsor
- University College DublinUniversity, hospital or other
- Collaborators
- Health Research Board, Ireland, Royal College of Surgeons, Ireland, Mater Misericordiae University Hospital, Beaumont Hospital, Rush University Medical Center
- Study start
- May 2016
- Primary completion
- Sep 2019 (actual)
- Study completion
- Sep 2019 (actual)
- First posted
- 22 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Antiretroviral therapy (ART) initiation is associated with a significant loss of bone mineral density (BMD), characterised by increases in bone turnover, which is largely limited to the first 48 weeks of therapy. Bisphosphonates, such as alendronate, decrease bone turnover and can limit loss of bone mineral density.
This study aims to determine if a short course of treatment with the oral bisphosphonate alendronate can limit loss of bone mineral density associated with initiation of ART in HIV-1 infected, antiretroviral naive, adult subjects.
Detailed description
Multi-centre, prospective, randomised, double-blind, placebo-controlled trial over 50 weeks. The aims of this study include:
- To determine if short-course treatment with alendronate versus placebo combined with calcium and vitamin D, initiated 2 weeks prior to start of ART and can prevent loss of BMD over 48 weeks of follow-up post ART initiation.
- To explore the effect of alendronate on bone turnover in the setting of ART initiation.
- To determine which factors, such as choice of ART, impacts the protective effect of alendronate in preventing BMD loss.
- To determine the relationship between changes in bone turnover markers, vitamin D, parathyroid hormone and calcium levels.
- To explore the pathogenesis of BMD loss with initiation of ART by investigating relationships between changes in immune function (T-cells and B-cells subsets), bone turnover and BMD.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alendronate | Active comparator | Drug: Alendronate, Dietary Supplement: calcium carbonate and colecalciferol, Drug: Tenofovir disoproxilAlendronate 70 mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada® |
| Placebo | Placebo comparator | Drug: Placebo, Dietary Supplement: calcium carbonate and colecalciferol, Drug: Tenofovir disoproxilPlacebo to alendronate 70mg plus calcium/vitamin D (1250 mg/400iu) plus Truvada® |
Who may qualify
- Ages
- 30 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- male>30 years old or female>35 years old
- HIV-1 antibody positive
- antiretroviral therapy naïve
- be presumed to have achieved peak bone mass
- be eligible for initiation of antiretroviral therapy in the opinion of the investigator
Key exclusion criteria (17 listed)
- subjects unable to comply with the study protocol or unable to stand/sit upright for at least 30 minutes
- history of osteoporosis
- history of fragility fracture or previous femoral fracture
- chronic renal failure
- hypocalcemia or hypercalcemia at screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlendronateAlso: Fosamax, Romaxalendronate 70 mg tablets to be administered weekly for a total of 14 weeks, commencing 2 weeks prior to ART initiation | Drug | Alendronate |
| PlaceboSugar pill manufactured to mimic alendronate 70 mg tablet administered weekly for a total of 14 weeks, commencing 2 weeks prior to ART | Drug | Placebo |
| calcium carbonate and colecalciferolAlso: Calcichew D3 forte, IdeosCalcium carbonate 1250 mg (equivalent to 500 mg of elemental calcium) and colecalciferol 400 iu (equivalent to 10 micrograms of vitamin D3) tablets administered twice daily for a total of 14 weeks, commencing 2 weeks prior to ART initiation | Dietary supplement | Alendronate, Placebo |
| Tenofovir disoproxilAlso: TruvadaEmtricitabine / tenofovir disoproxil fumarate 200 / 300 mg tablet administered once-daily with food (open-label) commencing 2 weeks after alendronate initiation and continuing for 48 weeks | Drug | Alendronate, Placebo |
Primary outcome
Rate of changes in bone mineral density
Time frame: 50 weeks
Between-group differences in percentage change in total hip, lumbar spine, femoral neck BMD and body composition to week 50 among subjects who received at least one dose of the study medication
2 secondary outcomes
Rate of changes in bone turnover markers
Time frame: 50 weeks
Impact of ART choice on alendronate protective effect
Time frame: 50 weeks
Results and safety
The study was stopped early (reason given: Due to the COVID-19 pandemic the study was terminated prematurely). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2022.
- Background: PubMed 25265073Cotter AG, Sabin CA, Simelane S, Macken A, Kavanagh E, Brady JJ, McCarthy G, Compston J, Mallon PW; HIV UPBEAT Study Group. Relative contribution of HIV infection, demographics and body mass index to bone mineral density. AIDS. 2014 Sep 10;28(14):2051-60. doi: 10.1097/QAD.0000000000000353.
- Background: PubMed 18025884McComsey GA, Kendall MA, Tebas P, Swindells S, Hogg E, Alston-Smith B, Suckow C, Gopalakrishnan G, Benson C, Wohl DA. Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV. AIDS. 2007 Nov 30;21(18):2473-82. doi: 10.1097/QAD.0b013e3282ef961d.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick WG Mallon, MB BCh BAO,PhD,FRCPI principal investigator
University College Dublin
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alendronate, calcium carbonate and colecalciferol and Tenofovir disoproxil in people with Bone Demineralization, run by University College Dublin at 2 sites in Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Due to the COVID-19 pandemic the study was terminated prematurely). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of changes in bone mineral density (time frame: 50 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02322099, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2022.