|Effects of LLLT|
Effects of Low Level Laser Therapy (LLLT)
And The Treatment of Periodontal Diseases
(Proposal for a clinical study prepared by
Dr. Rozana Vieru, DDS, MS, PhDc, Periodontist)
1. STUDY PURPOSE AND RATIONAL
The general objective of this study is to demonstrate that the application of low-level-laser therapy (LLLT) in addition to standard procedures employed to treat periodontal disease improves the outcome of the treatment.
Periodontal disease is an infectious process that is the leading cause of tooth loss in adults. It attacks the structures of the periodontium (the ligaments around the teeth), the gingivae, epithelial attachment, cementum that cover the root of the tooth, and the alveolar bone that supports the tooth. Periodontal disease causes a breakdown of the periodontium, resulting in loss of tissue attachment and destruction of the alveolar bone. Almost 75% of the American adults have some form of periodontal disease, and most are unaware of the condition. Certain systemic conditions increase the patient’s susceptibility to periodontal disease, and periodontal disease, in turn, may increase a patient’s susceptibility to certain systemic conditions. Disease-causing bacteria are necessary for the periodontal disease to begin, but they are not solely responsible for the destruction of the periodontium. Other risk factors can also alter the body’s response to the bacteria present in the mouth. These factors include traumatic occlusion, overhanging restaurations, sub-gingival placement of crown, orthodontic appliances or partial dentures may also contribute to the progression of the periodontal disease as well as smoking. Furthermore, the course of the disease is often influenced by other general medical factors, such as genetic preposition, specific medication, hormonal deregulation, systemic disease, some renal or hepatic conditions, diabetes, osteoporosis, metabolic calcium dysfunction, immune system deficiency, and stress.
Diabetes mellitus is a strong risk factor for periodontal disease. Diabetic individuals are three times more likely to have attachment and bone loss than non-diabetic patients. Furthermore, osteoporosis is always associated with alveolar bone loss. Women with osteoporosis have increased alveolar bone resorption, attachment loss, and tooth loss compared with women without osteoporosis. Estrogen deficiency has been linked to decreases in alveolar bone.
Tetracycline and non-steroidal anti-inflammatory drugs (NSAIds), have a beneficial effect on the periodontium. At the same time they have a very toxic effect on the liver which toxicity have a boomerang effect on the periodontium. Decreased salivary fluid (xerostomia) can be caused by more than 400 medications, including diuretics, antihistamines, anti-psychotics, anti-hypertension agents, and analgesics. Anti-seisure drugs and hormones such as estrogen and progesterone can cause gingival enlargement. Any of the above medications can accumulate to level of hepatic and renal toxicity, that will adversely affects periodontal tissue.
In this study we seek to study the effects of LLLT on marginal advance chronic periodontities (MACP) that have caused severe destruction of the periodontontal structures, i.e. clinical attachment loss over 5 mm. increased bone loss, increased pocket depth (usually 5 mm or grater) and increased tooth mobility. The symptoms of the disease are a red, swollen, tender gingiva, bleeding while brushing or flossing or spontaneous, loose or separating teeth, pain or pressure when chewing, pus around the teeth or gingival tissues,
The promising results of our prior clinical pilot studies involving human subjects with periodontal disease have provided the impetus for the proposed work. These studies showed that subjects receiving LLLT in addition to traditional treatment enjoyed markedly better recovery and healing than subjects treated without LLLT. LLLT resulted in shorter bleeding and pain recovery time, reduced post surgery complications (edema, inflammation, infection,), faster forming and maintaining of the clot, and better maintenance of the masticator functions. Overall we observed improved healing of the soft tissue, rapid recovery of a more compact bone tissue and fixation of the teeth, complete restoring and maintenance of the masticator and esthetic functions, with healthier gingival tissue. The effectiveness of LLLT varied somewhat as a function of the age, general health and metabolic problems of the patient. Very good results were obtained in diabetics for whom wound healing is usually a big problem.
2. STUDY DESIGN AND STATISTICAL ANALYSIS
We plan to recruit approximately 200 patients with marginal advance chronic periodontities. 100 of them are diabetic and another 100 show symptoms of osteoporosis. A correct diagnostic will be assessed based upon the medical and dental history. All these patients will be treated in a classical modern treatment. Approximately half of the diabetic patients and half of the patients with osteoporosis will receive LLLT in addition to the classical treatment. (The number of patients to be enrolled was determined by power calculations using the data obtained in our pilot studies.)
For all four groups ((1) diabetic with LLLT, (2) diabetic without LLLT, (3) osteoporosis with LLLT, and (4) osteoporosis without LLLT) we will determine the mean and standard deviations of the following parameters
§ 1. gingival bleeding time
§ 2. pain relief time
§ 3. bone recovery time
§ 4. inflammation
§ 5. complete healing
§ 6. recurrence
These parameters will be quantified as follows:
1. Bleeding time. We considered the gingival bleeding time as the time interval from the end of the curettage until the formation of the blood clot, established by the paper test. The time will be measured with a chronometer. The measurement will be performed in one location.
2. Pain relief time. Pain is a physiological consequence of the surgical trauma, accompanied by inflammation. We asked the patients to note the evolution of the pain intensity, and if they could use the maxillaries for normal mastication. The time interval described by the patient until the complete resolution of pain will be measured.
3. Bone recovery time. We determine the bone regeneration by observing the plague healing evolution (disappearing of the dental mobility, improving of the gingival color, recuperation of the masticator function and the comfortable state of the patient) and by evaluating X-ray images. When clinical parameters indicate bone recovery, we will perform the radiography. We considered as bone regeneration time the interval until the radiographs confirm the bone regeneratio.
5. Long term healing is quantified by
- rapid and aesthetic scar compared with photos,
- healing of the soft tissue and fixation of the tooth compare with photos
- tooth mobility measurements
- compare restoring of mastication and physiognomic functions and maintaining them with the patient journal and photos
6. The recurrence rate will be monitored and statistically quantify by the numbers: simply recurrence or no recurrence and the aggressivity of the recurrence.
For all these parameters we will perform an analysis of variances (ANOVA) and Bonferroni t-test to determine statistically significance in the differences of the mean values between the different cohorts. Statistical significance difference between patients treated with LLLT and not treated with LLLT is achieved and clinical usefulness of LLLT established if the corresponding p-values are smaller than 0,05.
3. STUDY PROCEDURE
For each subject participating in the study a complete detail diagnostic is made based on the dental and medical history. A periodontal examination will include the assessment of:
1. Plaque – which is the primary cause of the inflammation.
2. Calculus – which is hard mineralized plaque adherent on the surface of the teeth.
3. Gingival recession level, which can be visualized on the chart by drawing a dotted or colored line to indicate the gingival margin.
4. Bleeding index- severity of the gingival inflammation is measured by the amount of bleeding observed during probing. There are several indices to measure bleeding. Each system is based on the principle that healthy gingival do not bleed.
5. Measurement of the periodontal pocket occurs when the disease cause the normal gingival sulcus to become deeper than normal on the chart ( a normal sulcus is 3 mm or
6. Assessment of the bone level - Radiographs and probing measurements are used to assess the patient’s bone level. This may also be visualized on the chart by drawing a colored line to indicate the bone level. Radiographs detect inter-proximal bone loss, show the changes in the bone as the treatment progress, measure the crown to tooth ratio (the length of the clinical crown compared with the length of the root of the tooth) and show signs of traumatic occlusion .
The applied classic periodontal treatment consists of the following steps:
- Local and general anti-inflammatory prophylaxis;
- Elimination of the acute complains, such as pain, mastication problems, and edema;
- Rehabilitation and rebalance of the bite and oral dysfunctions;
- Parodontium and bone nutrition;
- Amelioration of the existing risk factors;
The surgical protocol consists in sub-gingival curettage that involves scraping or cleaning of the gingival lining of the pockets with sharp curette to remove necrotic tissue from the pocket wall. The periodontal surgery provides access to the root surface and allows to remove the infected tissue and to add nutrition direct to the bone by applying local collagen, hidroxy-apatite or bone graft, enzymes or antibiotics. After the surgical intervention, anti-inflammatory treatment will continued daily. Patients will be monitored at regular intervals over the course of 3 years.
For the LLLT we conceived an irradiation protocol following the data in the literature, and our experience. In general we will use an infrared diode laser type BF (EN 60 601-1), class 3B, safety class 1, with two laser beams, one infrared with a wave length = 830 nm, and another beam with a wave length = 630 nm. Convergent beam with energy between 0.5 and 3 J, will be applied continuously or in pulsed mode with a frequency of 4.68 Hz or 9.12 Hz. The parameters are adjusted depending upon the necessary penetration deep (2.5 – 12 mm).
LLLT starts immediately after surgical curettage, when we will apply laser irradiation on the bone, into the interdentally space, with no contact with the surgical plague, 0.5 J/ for each application, in pulsed mode. Before the suture, we irradiated again, into the external plain, in contact with the skin, with 2 J/cm^2, by scanning the entire operated area. Thirty minutes after the suture, we will apply1–4 J/cm^2, on each hemi-arcade area, the total dose being 4–16 J/cm2. The protocol it is individualized according to diagnosis. In the first three days after the surgery, we will irradiate the external plain at the same dose every day. In acute forms, we will apply a dose of 4J/ cm^2, every two days, in the first week, two sessions/ week, in the second week, and one session in the third week. In the following six months, we plan to apply one irradiation session monthly, at the same dose. In the chronic cases, the treatment is longer, performing more irradiation sessions, at smaller doses. The protocol is individualized upon the age and the heath status. LLLT is repeated every six months, in addition to the conventional local and general treatments used in periodontal disease prophylaxis and for boosting the immune system. We will evaluate the results by X-rays after six months, one year, and two years.
The intensity of the light by the irradiated tooth area is 10 to 30 mW/ cm^2, for about 10 seconds at each application. This light intensity is comparable to that emitted by a conventional laser pointer and is well below the threshold for injury (see Section on Risks). Transmitted light intensities will be 16-32 applications that also surround the maxillaries area and trigger points. Each session will take less than 20 minutes, including time for positioning. However, several applications at multiple locations may be necessary. It is expected that the entire procedure will require no more than 20 minutes. For each session will apply no more than 16J for that specific day.
4. STUDY DEVICE
For this study we will use an FDA approved LLLT system. The light intensities and exposure times are within required limits as set by the American National Standard Institute (ANSI) and recommended by the Occupational and Safety & Health Administration (OSHA) of the US Department of Labor. According to these standards (see ANSI Z136.1-2000, page 48, Table 7, entry for Visible and Near-Infrared light) the maximum permissible exposure (MPE) before any tissue damage occurs is given by MPE = 200x10^[0.002(-700)] mW/cm^2, where is the wavelength of the light. For example, at = 800 nm the MPE = 316 mW/cm^2, which is at least 10 times higher than intensities used in this study. Therefore, no adverse effects on the exposed tissues are expected.
We use a BTL infrared diode laser type BF (EN 60 601-1), class 3B, safety class 1, with two laser beams, one infrared with a wave length = 830 nm, and another beam with a wave length = 630 nm, convergent beam, energy between 0.5 and 3 J, applied continuously or in pulsed mode with a frequency of 4.68 Hz or 9.12 Hz. The parameters were adjusted depending upon the necessary penetration deep (2.5 – 12 mm). There will be 2 laser devises. One will be active and one will be blind having just a guided light that look similar to the active ray. To make sure that the trial is double blinded the operator and the subject will never know which laser is used , the active or the blind . Only Prof. Hielscher will assign a number to the patients and will keep secret the delegation of assign laser.
5. STUDY SUBJECTS
In order to be included in this study the subject must have been diagnosed belonging to the target group: Marginal Chronic Advanced Periodontities, that involved diabetics patients and subjects with osteoporose, and clinically healthy subjects that have MCAP by local factors only. There will be no restrictions based on gender, race or age, however only adult patients over age 18 will be recruited. We anticipate recruiting women and minorities in proportion to the demographic makeup of patients with MCP seeking treatment at Dental Clinical in the Columbia University Medical Center.
We will recruit approximately 200 subjects with Marginal Chronic Periodontal Disease in advanced stage. Dr. Vieru will put an exact diagnosis based on the status of the disease at the moment that the subject address to as, as well local and general, further blood tests , bone density and local tests will be proceed to both the control group and experimental group. In all cases, the primary physician of the patient will diagnoses and supervise the patient treatment and have to agree that the patient is suitable for the study and ascertain from the patient that the he/she is willing to discuss the study with the research team before any approach may be attempted by the investigators.
7. CONFIDENTIALLITY OF STUDY DATA
All study data is coded according to the order and the date a patient participated in the The data is stored on a computer workstation The computer and data are only accessible by the PI and his co-investigators. The PI will maintain a master list that links human subject names to the particular data, on a separate storage device located in the PI’s. No other persons will have access to that information.
8. POTENTIAL RISKS
The LLLT performed in this study present no known hazards. Unlike X-rays, the energy from light sources used in this study are non-ionizing and the tissue will not be damaged. The light intensities and exposure times will be within required limits as set by the American National Standard Institute (ANSI) and recommended by the Occupational and Safety & Health Administration (OSHA) of the US Department of Labor. According to these standards the maximum permissible exposure (MPE) before any tissue damage occurs is given by MPE = 200x10^[0.002(-700)] mW/cm2, where (lambda) is the wavelength of the light used in the study (see ANSI Z136.1-2000, page 48, Table 7, entry for Visible and Near-Infrared light). For example at = 830 nm, a typical wavelength to be used in the study, the MPE = 316 mW/cm2, which is at least 10 times higher than intensities used in this study. Therefore, no adverse effects on the tissue exposed to light are expected. All operators personal and the subjects are to ware protective goggles at all time while operating the LLLT devise to avoid accidental eye exposure.
9. POTENTIAL BENEFITS
Participating subjects will benefit from the classical modern and complete dental treatment of their periodontal disease. We expect that patient treated in addition with LLLT will further benefit from improved healing times, less pain, and less bleeding. In addition general social benefits can be expected, if the study leads to the development of a novel LLLT modality for treatment of periodontal disease, which allows early noninvasive treatment for periodontal affection and other diseases. In addition the optical technology promises to be more cost effective and may reduce the cost of patient care.
The LLLT is offered in addition to standard clinical methods in the treatment of periodontal disease. There are no other alternative treatments and therefore, the alternative to participating in this study is simply not to participate.