Do you have a MISSING TOOTH? Do you want to replace it ... · Do you want to replace it with a DENTAL IMPLANT? ... Study treatment will be rendered at no cost to volunteers. Only

V01 25th Feb 2016 V01 25th Feb 2016

V3.0 10 Apr 2017

Do you have a MISSING TOOTH?

Do you want to replace it with a DENTAL IMPLANT?

The Centre for Oral Clinical Research at Barts Health, under the supervision of Professor Nikolaos Donos,

is recruiting POST MENOPAUSAL OSTEOPOROTIC WOMEN

for a research study that will evaluate the stability of jaw bone around dental

implants.

Post menopausal women >50 years of age, with a diagnosis

of osteoporosis and with a missing tooth may be eligible to participate in this study.

The study consists of a total of 8 visits over

a 15-months period.

Study treatment will be rendered at no cost to volunteers.

Only one implant will be provided as part of the study, although we will provide you and your dentist with a comprehensive dental report, where we

will advise you on any other dental problems you may have.

If you are interested in participating in this study and you would like to learn more,

please contact Dr Elena Calciolari via phone at 0207 882 5135

or Lisa Groarke at 0207 882 8641 Email: [email protected]

Patients diagnosed with osteoporosis on bone density scanning do not always require treatment. Your scan will be reported by one of our consultant

rheumatologists back to the doctor who referred you taking into account your medical history. You should discuss with the doctor who referred you for the scan whether

you need treatment. We will provide you today with some information on Osteoporosis for you to take away to read.

mailto:[email protected]

Subject’s initials _______

Version 2.2; 19-May-2017 Study Number: COCR-0001 Patient Identification Number______

PARTICIPANT INFORMATION SHEET

Title of project: Radiographic peri-implant alveolar bone changes in post-menopausal osteoporotic women Name of Chief Investigator: Prof. Nikolaos Donos Please read this sheet carefully. Please ask if you do not understand or would like more information PART 1

1 Invitation to participate You are being asked to participate in a research project being conducted with the approval of London Bridge Research Ethics Committee. Before you decide we would like you to understand why the research is being done and what it would involve for you. One of our team will go through the information sheet with you and answer any questions you have. We‘d suggest this should take about 15 minutes. (Part 1 tells you the purpose of this study and what will happen to you if you take part. Part 2 gives you more detailed information about the conduct of the study). Please feel free to discuss with friends and family and ask us if there is anything that is not clear, or if you would like more information.

2 What is the purpose of this study? This study aims to evaluate the possible impact of post-menopausal osteoporosis on the healing of the jawbone around a dental implant with a modified titanium surface.

Despite some contradictory results, in animal studies a reduced and delayed integration of dental implants into the alveolar (jaw) bone have been reported. Very little human data is available and, although most of the published studies support the applicability of implants in osteoporotic patients, there are data suggesting that osteoporosis might be associated to a lower implant success rate, especially in case the bone around dental implants is of insufficient quantity and has to be regenerated.

In the past years, a considerable amount of literature has grown up on the development of titanium surfaces with modified properties with the aim to improve the integration of dental implants into the jawbones. These surfaces may be particularly beneficial in patients affected by systemic diseases and in cases of poor-quality jawbone, such as in osteoporotic patients. In this study we want to study the bone levels around dental implants with a modified surface (SLActive) that should stimulate and accelerate bone

INSTITUTE OF DENTISTRY

CENTRE FOR ORAL CLINICAL RESEARCH TURNER STREET LONDON E1 2AD Professor Nikos Donos Centre Head Professor of Periodontology & Implant Dentistry Tel: 02078828641 E-mail: [email protected]


2


formation. The hypothesis is that this surface should promote faster bone formation around the implants and allow achieving stable peri-implant bone levels 12 months after implant loading (i.e. positioning of a crown on top of the implant) in post-menopausal osteoporotic women.

3 Why have I been invited? You have been invited to take part into this study as you have been diagnosed with post-menopausal osteoporosis and you may have a missing tooth that can be replaced with a dental implant. Our aim is to recruit 20 women with post-menopausal osteoporosis that need a tooth to be replaced with a dental implant.

4 Do I have to take part? It is up to you to decide whether or not you would like to take part in this study. We will describe the study and go through this information sheet. If you are eligible and agree to take part, you will be given this information sheet to keep and will be asked to sign a consent form. If you do not wish to participate, you would not be required to attend the research unit at the Centre for Oral Clinical Research at the Barts Health NHS Trust Dental Hospital for the examination, but you would continue with any regular care already planned either through the Barts Health NHS Trust Dental Hospital or through your regular dentist.

5 What will happen to me if I take part? This study consists of eight visits. All visits will take place at the Centre for Oral Clinical Research at the Barts Health NHS Trust Dental Hospital in Whitechapel.

Visit 1 Enrolment (45 minutes):

Informed consent for the full study will be obtained;

Recording of medical / dental history;

Saliva sample collection (you will be asked to spit in a plastic tube);

Examination of the teeth and gums with a blunt probe gently placed in the gap between the teeth and the gums (Basic Periodontal Examination, BPE). If BPE≥3, which means that you have deep pockets and bone loss around your teeth, a full mouth 6-points pocket chart will be performed. This means that, with the help of a blunt probe, probing pocket depth – PPD – and gum recession – REC – will be measured in 6 points around each tooth, together with the evaluation of furcation involvement (i.e. bone loss up to the area where roots divide in molars and premolars) and tooth mobility.

Clinical measurement of periodontal parameters in the teeth adjacent to the area where the implant will be placed. In particular, the presence of plaque (PI), bleeding during probing (BOP), gum recession (REC) and the presence of pockets (PPD) will be recorded;

3D facial scan (it is a radiation-free and contact-free 3D image of your face and it takes 1.5 milliseconds to take it).

Visit 2 Full mouth debridement (60-90 minutes) (within 90 days from enrolment):

Recording of changes in medical / dental status and any new medications;

Recording of any adverse event (AE) (i.e. undesirable experience);

3


Full-mouth plaque and bleeding scores (FMPS, FMBS)

Oral hygiene instructions and debridement of all teeth above and under the gums (as necessary). Local anaesthesia may be used as required to ensure pain control; In case you require further treatment, this will be arranged outside the study protocol. No implant will be placed until the infection around your gums is under control (no pockets ≥5 mm) will be reached.

In order to plan the implant placement and according to the clinician’s judgment and the complexity of the case, either a CBCT scan (low-dose 3D x-ray) or a peri-apical intra-oral x-ray, limited at the area of the implant placement, will be taken.

Visit 3 Implant placement (60-90 minutes) (within 90 days from Visit 2):


Recording of any AE;

Implant placement. If required, simultaneous bone regeneration around the implant will be performed with the help of biomaterials (a collagen membrane and a bone graft);

Recording of maximum torque (it is a number that expresses of the stability of the implant inside the bone) during implant placement;

Resonance frequency analysis (it evaluates the stability of the implant inside the bone);

3D facial scan;

CBCT scan (i.e. low-dose 3D radiograph) in the area of the implant. This will be done either the same day of the implant placement or within the following 10 days.

Visit 4 Suture removal (15-30 minutes) (7 days + 3 days after Visit 3):



Clinical evaluation of soft tissue healing (look at the surgical site and report of any complication);

Saliva and peri-implant crevicular fluid collection (a tiny strip will be gently inserted around the implant for 30 seconds to collect the peri-implant crevicular fluid);

Suture removal;


3D facial scan; CBCT scan (i.e. low-dose 3D radiograph) in the area of the implant, if not performed on the day of the implant placement. In case bone regeneration was performed simultaneously to implant placement, the suture removal will be performed 14 days ±5 days after implant placement.

Visit 5 Implant impression (30 minutes) (6 weeks ± 7 days from Visit 3)



Implant impression;


3D facial scan.

4


In case bone regeneration was performed simultaneously to implant placement, the implant impression will be taken 11 weeks (+7 days) after implant placement.

Visit 6 Implant loading (30 minutes) (8 weeks ± 7 days from Visit 5)



Clinical measurement of the periodontal parameters in the teeth adjacent to the implant (PI, BOP, REC and PPD);

Implant loading (i.e. positioning of a crown on top of the implant) and control that the mastication is correct;


Peri-apical X-ray to check the correct position of the crown over the implant. In case bone regeneration was performed simultaneously to implant placement, the implant loading will be done 12 weeks (+7 days) after implant placement.

Visit 7 6-months follow-up (20 minutes) (6 months ± 14 days from Visit 6)



Saliva and peri-implant crevicular fluid collection;


Full-mouth six-points pocket chart (PPD, REC, mobility, furcation);

Polish and oral hygiene instructions;

Resonance frequency analysis (it evaluates the stability of the implant inside the bone). Visit 8 12-months follow-up (30 minutes) (12 months ± 14 days from Visit 6)




Full-mouth six-points pocket chart (PPD, REC, mobility, furcation);

Polish and oral hygiene instructions;


CBCT scan (i.e. low-dose 3D radiograph) in the area of the implant.

Photographs of the mouth may be taken for documentation purposes. Individuals will not be identifiable from these photos.

6. What will I have to do?

You will be asked to attend all the 8 scheduled visits in order to complete the study. You will be also asked to inform our team in case your general health conditions changes or you need to take new medications or other over-the-counter drugs, as some of these could affect the results of the study and you may therefore have to exit the study. Since in Visit 1, 4 and 7 a saliva sample will be collected (at visit 4 and 7 also the peri-implant

5


crevicular fluid will be collected), you will be asked not to eat, smoke, drink, or perform oral hygiene for at least 60 minutes prior to the sample collection.

7 Risks and discomfort Dental/periodontal examinations performed during the screening and the enrolment visits, non-surgical debridement of the teeth, dental anaesthesia injections, implant placement and implant impression may involve some discomfort, but they are part of routine dental procedures. If we detect signs of disease worsening over the study period, you will be treated with the standard required therapy. If extensive treatment would be indicated, you may be withdrawn from the study and your GP will be informed. CBCT scans and peri-apical x-rays are not usually associated with discomfort and will be focused only in the implant area. All the procedures you will undergo are part of routine dental treatments. The only procedure you would not

necessary undergo if you didn’t take part into the study are the CBCT scans after implant placement and at

12 months after positioning the crown over the implant. However, by using the new generation of CBCT scanners it is possible to greatly reduce the radiation dose delivered and to limit the radiation exposure only to the region of the implant. In addition, the information resulting from the CBCT scans will be of great value to check the correct positioning of the implant and to intercept any problem that may have occurred during the implant placement and 12 months after loading the implant. In fact, CBCT scans allow us to precisely measure the height and width of the jawbones and to check for the proximity with important structures. The 3-D facial scan is a non-invasive, contact-free and radiation-free facial image capturing process. It takes less than a second, almost like having a passport photo. However, it does require some adjustment of the head position, therefore, the complete scanning procedure may take up to 5-10 minutes. It is a quick and very straight forward process. You will be asked to sit up straight on an adjustable chair for a few minutes as shown in the picture below:

The saliva collection is done by spitting into a plastic tube and is not associated to any risk or discomfort. The peri-implant crevicular fluid is collected by gently inserting a tiny strip around the implant for 30 seconds and is not associated to risk or discomfort.

6


The samples collected during the study may be stored after the end of the project and additional analyses may be performed following the results of the study. Surgical complications The risk of damaging surrounding structures, such as other teeth, blood vessels or nerves during implant placement will be minimized by carefully planning the surgery and by the use of x-ray images (CBCT or peri-apical intra-oral x-ray). Any of these risks will be discussed in details with the therapist/principal investigator during the pre-operative treatment planning, as part of standard of care. Implant success and survival Dental implants have a high success and survival rate, >90% at 10 years. It is not clear if osteoporosis reduces the survival of dental implants and only a few studies have been published until now. Poor oral hygiene (tooth brushing) and smoking can significantly reduce the success of dental implant treatment and increase the risk of complications. In particular, accumulation of plaque (bacteria) around the implant may cause a complication called peri-implantitis. It is typically associated to bone loss around the implant and inflammation of the gum around it. If not treated, it can cause the loss of the implant. Therefore, it is of great importance that you keep your implants and teeth clean (by using toothbrush and floss/interdental brushes) and you attend regular visits with your dentist. Antibiotic therapy will be prescribed to reduce the risk of infections after the implant placement, as part of standard of care.

Complications associated to osteoporosis Following a dental surgical procedure such as a dental extraction or a dental implant placement, or even spontaneously, osteoporotic patients in treatment with bisphosphonates or denosumab may develop a rare complication called osteonecrosis of the jaw (ONJ). ONJ presents as an area of bone that does not heal properly for long periods and can be associated to infection and pain. The risk of developing a ONJ is very

rare (10 cases in 1,000 – 10,000 people) and can be minimized by adopting some precautions, such as by

prescribing antibiotic therapy, reducing the surgical trauma, suturing the gum back in position and prescribing appropriate post-surgical instructions. The risk of developing ONJ seems to increase in people that take these medications for long periods and this is why in this study we do not include patients taking bisphosphonates or denosumab for more than 4 consecutive years. In the remote chance that ONJ occurs, you will receive treatment, which will include the use of antibiotics and may involve the removal of the implant.

8. Radiation Regulations

By taking part into this study, you will be exposed to a total dose of radiation of approximately 0.13 mSv, which is considered a trivial dose and carries a minimal life-time risk of fatal cancer of about 1 in 150,000. It is equivalent to approximately three weeks of normal background radiation.

9 Possible benefits for participants You will benefit from a full-mouth diagnosis of hard and soft tissues, the careful removal of plaque and tartar above and under the gums, detailed oral hygiene instructions and the replacement of a missing tooth with a dental implant in a highly controlled research environment, by specialised dentists, at no cost. In the case that

7


you need additional periodontal treatment, this will be arranged outside the study protocol but within Barts Health NHS Trust Dental Hospital. These procedures will not be paid for by the study. In addition, the information we get from this study will likely help improve the treatment outcomes of people with osteoporosis in the future. Only one implant will be provided (for free) as part of the study. If you have other missing teeth, we cannot replace them as part of this study. We can advise both you and your dentist on the different options to replace them (this may not necessarily imply the use of implants), but we cannot offer you the treatment (additional implants). The cost of replacing a missing tooth with a single implant in a private practice can indicatively vary from 1000 to 5000 £.

10. What happens when the research study stops Your dentist will be informed for any further treatment required and given a detailed report of your oral health and of the treatments provided during this study. At the end of the study, your samples (saliva and peri-implant crevicular fluid) might be used for further analyses for the benefit of dental research. In this case, a new ethical approval will be requested before doing any new analysis.

11. Will my taking part in the study be kept confidential?

Yes. We will follow ethical and legal practice and all information about you will be handled in confidence. The details are included in Part 2.

If the information in Part 1 has interested you and you are considering participation, please read the additional information in Part 2 before making any decision.

PART 2

12. What if relevant new information becomes available?

Sometimes we get new information about the treatment being studied. If this happens, your research team might consider you should withdraw from the study. We will explain the reasons and arrange for your care to continue.

13 Voluntary participation and right to withdraw

Your participation in this study is voluntary. You can take as much time as you need to decide upon taking part in this study. You may refuse to participate or may discontinue participation from the study at any time without any negative effects. Not taking part in the study will not affect the care you receive at Barts Health. All information about your medical records will be treated as strictly confidential and will be used only for medical purposes. Your medical records may be inspected by competent authorities and properly authorized persons, but if any information is released this will be done in a coded form so that confidentiality is strictly maintained. Participation in this study will in no way affect your legal rights.

14. Complaints

8


Every care will be taken in the course of this research project. If you have a concern about any aspect of this study, you should ask to speak to the researchers, who will do their best to answer your questions (Tel 02078828641). If you remain unhappy and wish to complain formally the normal National Health Service complaints mechanisms are available to you. Please ask your study doctor if you would like more information on this and the Barts and the London NHS Trust complaints procedure. You can access Bartts Health Patient Advice and Liaison Service (PALS) by: Tel: 020 3594 2040 Email: [email protected]

If you are harmed by taking part in this research project, there are no special compensation arrangements. If you are harmed as a result of someone’s negligence, you may have grounds for legal action for compensation against Barts and the London NHS Trust, but you may have to pay for your legal costs. The normal National Health Service complaints mechanisms will still be available to you (if appropriate).

15 Confidentiality The investigators will make every possible effort to keep your personal information confidential. Personal data will be stored securely at Barts Health NHS Trust and only anonymised data will be transferred to QMUL (the sponsor). You will be assigned a study ID number upon enrollment into the study, which will be used to anonymise data collected from you. Only clinicians that are involved in your direct care will have access to your medical notes. The principal investigator is responsible for safety and security of the data. Medical records, which identify you and the consent form signed by you, may be inspected by an Institutional Review Board or Ethical Review Committee. The results of this research project may be presented at meetings or in publications; however, any research data released or published will not identify volunteers by name.

16 Involvement of the General Dental Practitioner (GDP) and General Practitioner (GP)

If you agree to participate your General Dental Practitioner, as well as your General Practitioner, will be informed of your involvement in this study. The GDP will also be sent a summary of the results of the dental exam.

17 Study results

The results of this study may be presented at meetings and may be published, probably at least one year after the end of the project. No participants will be identified in any report. If you would like to receive the results of the study, please write to the Principal Investigator, Prof. Nikolaos Donos.

18. Who Is organising and funding the research?

The Straumann Institute is funding this research project. Queen Mary University of London (QMUL) is sponsoring and organizing this study.

19 Ethical approval of the study


9


Research in the NHS is looked at by independent group of people, called a Research Ethics Committee, to protect your interests. This study has been reviewed and given favourable opinion by London Bridge Research Ethics Committee.

20 Whom to Question Regarding this Study

You have the right to ask questions about this study at any time. You will be informed about any change to the study which might concern you. Should you have questions, please contact Prof. Nikolaos Donos and the team by email on [email protected] or by phone on 02078828641.

A copy of this information sheet and a signed consent form will be given to you.

Chief Investigator: Professor Nikos Donos, Head Clinical Oral Research Centre, Chair Periodontology & Implant Dentistry, Institute of Dentistry, Barts & the London School of Medicine & Dentistry, QMUL, London, E1 2BA.

[email protected]



Inclusion Criteria Each participant must meet the following inclusion criteria to be enrolled in the study:

• Participants must present a diagnosis of osteoporosis based on DXA measurement of the bone mineral density at the femur neck and/or total hip and/or lumbar spine (T value 2.5 SD or more below the young female adult mean) within the past 24 months.

• Not in treatment with anti-resorptive agents (like bisphosphonates and denosumab) for more than 4 consecutive years, in order to reduce the risk of medication-related osteonecrosis of the jaws (Lo et al., 2010).

• ≥ 50 years old.

• In self-reported menopause, defined as the permanent cessation of ovulation, for at least one year (Soules et al., 2001).

• Edentulous area involving a maximum of two teeth (wisdom teeth and second molars are excluded) and presenting at least one neighbouring tooth (e.g. gap in the area of a second premolar and first molar, with first premolar in place).

• Residual alveolar width ≥ 4 mm at bone level (Milinkovic and Cordaro, 2014), residual alveolar height >8 mm, enough inter-arch space for a crown (at least 5 mm) and a minimum distance of 7 mm from the adjacent teeth (Shah and Lum, 2008). The width and height will be confirmed after x-ray examination in Visit 2.

• Possibility to restore a functional occlusion with a minimum of four occlusal units (i.e. pairs of occluding posterior teeth).

• Willingness to replace the missing tooth/teeth with dental implants

• Registration with a GDP.

Exclusion criteria

Participants will not be eligible for participation in the study if:

• On chronic treatment (i.e., two weeks or more) with any medication severely affecting oral status (e.g. participants with gingival hypertrophy caused by anti-epileptics, calcium antagonists, cyclosporine and other immunosuppressive) or bone metabolism (e.g. anticoagulant medications, long-standing steroid medications – i.e. equal or more 2.5 mg of prednisolone a day taken for more than 3 months -, anticonvulsants, immunosuppressants).

• Affected by systemic diseases recognized to severely affect bone metabolism (e.g. Cushing's syndrome, Addison's disease, diabetes mellitus type 1, leukaemia, pernicious anaemia, malabsorption syndromes, chronic liver disease, rheumatoid arthritis).

• Knowingly affected by HIV or viral hepatitis.

• History of local radiation therapy in the last five years.

• Affected by limited mental capacity or language skills such that study information cannot be understood, informed consent cannot be obtained, or simple instructions cannot be followed.

• Presenting an acute endodontic/periodontal lesion in the neighboring areas to the implant site.

• Completely edentulous

• With evident severe atrophy of the alveolar ridge that could preclude an implant placement (e.g. sharp knife edge ridge)

• Severe bruxism or clenching habits

• Smokers of > 5 cigarettes a day.

• A daily alcohol intake >2 units/day.

• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality which may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this trial.

• Patients unable or not willing to return for follow-ups.

Documents

Do you have a MISSING TOOTH? Do you want to replace it ... · Do you want to replace it with a DENTAL IMPLANT? ... Study treatment will be rendered at no cost to volunteers. Only