Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202407466904092 Date of Approval: 26/07/2024
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title A Randomized, Double Blind, Single Centre, study to assess the efficacy, safety and tolerability of the Gastrin Receptor Antagonist (GRA), Netazepide administered for 90 days, in post-menopausal women (OSTEO-GRA)
Official scientific title A Randomized, Double Blind, Single Centre, study to assess the efficacy, safety and tolerability of the Gastrin Receptor Antagonist (GRA), Netazepide administered for 90 days, in post-menopausal women (OSTEO-GRA)
Brief summary describing the background and objectives of the trial Osteoporosis is a common and costly disease which carries a significant morbidity and mortality [1]. In South Africa, the incidence of osteoporosis in the white, Asian and mixed-race populations appears similar to that of developed countries. Overall, the lifetime risk of a fracture in South African women is estimated as 30%. Up to 20% of hip fracture victims die within one year, and more than 50% never regain the functional ability to lead an independent life. Oestrogen deficiency is a key factor in postmenopausal osteoporosis. Levels of oestradiol decrease by 90% at the menopause and this is associated with a doubling in bone turnover along with accelerated bone loss. Recent data demonstrate that a combination of loss of oestrogen and stomach function act in concert to elevate circulating levels of plasma gastrin which is responsible for inhibition of bone metabolism based upon the activation of gastrin receptors on bone cells. This finding is novel and important current agents to treat osteoporosis, including agents other than anti-oestrogenics, are not always effective.We hypothesize that osteoporosis is due to oestrogen deficiency and gastrin excess (due to gastric mucosal atrophy). Osteoporosis therefore can be induced by gastrin and reversed by a gastrin receptor antagonist (GRA). Typically, bone turnover markers are evaluated as surrogate markers for treatment responses. The National Bone Health Alliance advocates measurements of collagen type 1 cross-linked C-telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP). Primary Objective: To examine the effect of the GRA on CTX levels in post-menopausal women.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) OSTEOGRA
Disease(s) or condition(s) being studied Musculoskeletal Diseases
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Prevention
Anticipated trial start date 01/04/2019
Actual trial start date 02/01/2020
Anticipated date of last follow up 31/07/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 90
Actual target sample size (number of participants)
Recruitment status Closed to recruitment,follow-up continuing
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Netazepide 100 mg daily given as four 25 mg capsules (orally) after breakfast 90 days Netazepide capsules 45
Control Group Placebo Matching placebo capsules are to be taken orally in the morning as four placebo capsules after breakfast 90 days Matching placebo 45 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
A participant must meet the following criteria to be eligible for inclusion in the study: 1. Women >5 years post-menopausal or who have had an oophorectomy 2. FSH levels of >40 IU/L (the FSH level precludes premenopausal women and those who may have FSH-related bone losses) as determined at the screening visit. 3. Participants with no clinical or biochemical evidence of secondary causes of bone loss (Appendix 1). 4. Participants must not be taking medications (see Appendix 6) that have an action on bone metabolism A participant who meets any of the following criteria will be excluded from the study: 1. Participants with confirmed diagnoses according to their medical history from diseases with a known propensity to result in secondary bone loss that might cloud the assessment of disease naïve osteoporosis. It includes Diabetes Mellitus, thyroid dysfunction (TSH outside the reference range), IBD, celiac disease, pancreatic exocrine insufficiency, epilepsy, hyperparathyroidism. (Appendix 1) 2. Participants who have had a bone fracture in the previous year. (Appendix 1) 3. Participants who have had orthopaedic surgery in the previous year. (Appendix 1) Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 55 Year(s) 99 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 17/05/2019 University of Cape Town Faculty of Health Sciences Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Room E53-45 Old Main Building, Groote Schuur Hospital, Observatory Cape Town 7925 South Africa
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome CTX levels in post-menopausal women before and after GRA administration Baseline, Day 7, Day 28, Day 56, Day 90, Day 180
Secondary Outcome Bone resorption: NTX (urine) and serum TRAP levels Baseline, Day 7, Day 28, Day 56, Day 90, Day 180
Secondary Outcome Individual biomarkers PINP, Osteocalcin and Alk Phos Baseline, Day 7, Day 28, Day 56, Day 90, Day 180
Secondary Outcome Bone balance: To determine whether the GRA has an effect on bone balance, we will calculate the ratio of CTX/PINP at baseline and each of the 4 follow-up time points Baseline, Day 7, Day 28, Day 56, Day 90, Day 180
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Groote Schuur Hospital L51 Old Main Building, Groote Schuur Hospital, Observatory Cape Town 7925 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
CL Biosciences 2-14 Finch Road, Douglas, Isle of Man IM1 Douglas IM1 United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Cape Town Bremner Building, Lovers Walk, Rondebosch Cape Town 7700 South Africa University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Stuart More stuart.more@uct.ac.za +27214044169 Groote Schuur Hospital, Observatory
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Principal Investigator
Role Name Email Phone Street address
Public Enquiries Stuart More stuart.more@uct.ac.za +27214044169 Groote Schuur Hospital, Observatory
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Stuart More stuart.more@uct.ac.za +27214044169 Groote Schuur Hospital, Observatory
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Sponsor will provide Individual participant data that underlie the results reported in the Clinical Study Report, after deidentification (text, tables, figures, and appendices) Clinical Study Report,Statistical Analysis Plan,Study Protocol Within 12 months from end of study Requests for access to the raw data (deidentified) will be considered for researchers who provide a methodologically sound proposal, on a case-by-case basis by the PI and in consultation with the ethics committee.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 18/07/2024 As requested. Primary Objective: To examine the effect of the GRA on CTX levels in post-menopausal women. Secondary Objectives 1. To examine the temporal change in bone markers to provide information relating to remodelling imbalance. 2. To examine the reversibility of the GRA treatment on markers of bone formation and bone resorption. 3. To examine the safety and tolerability profile of GRA in postmenopausal women. Osteoporosis is a common and costly disease which carries a significant morbidity and mortality [1]. In South Africa, the incidence of osteoporosis in the white, Asian and mixed-race populations appears similar to that of developed countries. Overall, the lifetime risk of a fracture in South African women is estimated as 30%. Up to 20% of hip fracture victims die within one year, and more than 50% never regain the functional ability to lead an independent life. Oestrogen deficiency is a key factor in postmenopausal osteoporosis. Levels of oestradiol decrease by 90% at the menopause and this is associated with a doubling in bone turnover along with accelerated bone loss. Recent data demonstrate that a combination of loss of oestrogen and stomach function act in concert to elevate circulating levels of plasma gastrin which is responsible for inhibition of bone metabolism based upon the activation of gastrin receptors on bone cells. This finding is novel and important current agents to treat osteoporosis, including agents other than anti-oestrogenics, are not always effective.We hypothesize that osteoporosis is due to oestrogen deficiency and gastrin excess (due to gastric mucosal atrophy). Osteoporosis therefore can be induced by gastrin and reversed by a gastrin receptor antagonist (GRA). Typically, bone turnover markers are evaluated as surrogate markers for treatment responses. The National Bone Health Alliance advocates measurements of collagen type 1 cross-linked C-telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP). Primary Objective: To examine the effect of the GRA on CTX levels in post-menopausal women.
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 22/07/2024 As requested by reviewer. Sponsor will provide a link to summary results publicly within 6 months to 1 year. Sponsor will provide Individual participant data that underlie the results reported in the Clinical Study Report, after deidentification (text, tables, figures, and appendices)
Section Name Field Name Date Reason Old Value Updated Value
Reporting Key access criteria 22/07/2024 As requested by reviewer. Requests for access to the raw data will be considered on a case-by-case basis by the PI and in consultation with the ethics committee. Requests for access to the raw data (deidentified) will be considered for researchers who provide a methodologically sound proposal, on a case-by-case basis by the PI and in consultation with the ethics committee.
Section Name Field Name Date Reason Old Value Updated Value
Reporting Study protocol document 04/12/2024 Statistical Analysis Plan now available. Study Protocol, Clinical Study Report Study Protocol, Statistical Analysis Plan, Clinical Study Report
Section Name Field Name Date Reason Old Value Updated Value
Reporting Study protocol document 22/07/2024 As requested by reviewer. Clinical Study Report Study Protocol, Clinical Study Report