CClinicalTrials.gg
CompletedNCT03454581TMDPBMTUpdated Sep 26, 2019Results posted

Effectiveness of Photobiomodulation and Manual Therapy Alone or Combined in TMD Patients

A Phase 2 interventional study of Photobiomodulation and Manual Therapy (MT) in Temporomandibular Disorder, sponsored by Federal University of Rio Grande do Sul. Completed. Open to participants aged 21 Years and older. Per ClinicalTrials.gov, last updated 2019-09-26.

Sponsored by Federal University of Rio Grande do Sul · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
51
Allocation
Randomized
Ages
21 Years and older
Sex
All
01

Study summary

The aim of the present study was to investigate the effect of photobiomodulation (PBM) and manual therapy (MT) isolated or combined in the reduce of pain, the improve of mandibular movements, the psychosocial aspects and the anxiety symptoms of patients with TMD.

Read the detailed description

Temporomandibular disorders (TMD) is a complex and multifactorial disease. Therapeutic modalities, as PBM and MT, expected to relief of symptoms, improve of function and reduce the impact of the disease in patient's life. Fifty-one TMD patients were randomly allocated to three groups: PBM group (n=18) using 808 nm, 100 milliwatt (mW), 13.3 J ∕cm2, 4 J per point), MT group (n=16) with 21 minutes sessions of MT of the masticatory muscles and TMJ and Combined Therapy group (CT) (n=17) applying the 2 protocol described above. All treatments were done three times a week for four consecutive weeks. Evaluations were performed at baseline, during the treatment (days 7, 14, 21, and 28) and follow up (day 60 and day 90). Visual analogue scale (VAS), Research Diagnostic Criteria (RDC/TMD) Axis I and II, Beck anxiety inventory (BAI) were used in different moments of evaluation time.

02

Conditions studied

  • Temporomandibular Disorder

Keywords

  • Temporomandibular Diseases
  • Photobiomodulation
  • Low level laser
  • Treatment
  • Manual Therapy
03

Who can participate

Ages eligible
21 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • TMD myogenic and arthrogenic diagnosis based in RDC/TMD Axis I analysis
  • Pain in temporomandibular joint (TMJ)
  • Limitation in mouth opening.

Exclusion criteria

Exclusion Criteria:

  • Current dental or physical treatment
  • Polyarthritis and other rheumatic diseases
  • Use of anti-inflammatory and muscle relaxant
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Outcomes assessor)
Enrollment
51 participants (actual)

Study arms

  • Experimental
    Photobiomodulation group (PBM)

    Gallium-aluminium-arsenide (GaAlAs) diode laser (MM Optics Recover, São Carlos, São Paulo, Brazil) with a wavelength of 808 nm, punctual contact mode,spot size of 0.03 cm2, power output of 100 mW, output density of 333 mW∕cm2, energy density of 13.3 J ∕cm2, 40 s exposure time per point, and 4 Joules (J) of total energy per point. 18 individuals

    Procedure: Photobiomodulation

  • Experimental
    Manual Therapy group (MT)

    At masticatory muscles were performed circular movements, slip and compression with fingers movements. At the temporomandibular joint (TMJ) was performed a caudal distraction with anterior projection, placing the thumb on the second or third molar. 16 individuals.

    Procedure: Manual Therapy (MT)

  • Experimental
    Combined therapy group (CT)

    Applied the protocols of PBM group and immediately after, to MT group. 17 individuals.

    Procedure: Photobiomodulation · Procedure: Manual Therapy (MT)

Interventions

  • ProcedurePhotobiomodulation

    PBM was applied, three times a week for four consecutive weeks at 5 points in the TMJ region: superior, anterior, lateral, posterior and postero inferior to the condyle. In addition, all patients received laser application in the temporal muscle (anterior, middle and posterior), in the masseter (upper, middle and lower portion) and insertion of the medial pterygoid.

    Also known as: Low Level Laser (PBM)

  • ProcedureManual Therapy (MT)

    Patients were submitted to MT at temporal, masseter and pterygoid medial from both sides, during 3 minutes each muscle group (Extraoral) and at masseter and lateral pterygoid (Intraoral) for 3 minutes, each total 21 minutes. MT on the TMJ region was performed for 1 minute and 3 repetitions during three times a week .

05

What researchers measure

Primary outcomes

  1. Change From Baseline in Visual Analogic Scale (VAS) for Pain

    Visual Analogic Score (VAS) is a psychometric scale used to measure subjective characteristics, as pain. Consists of a 100mm horizontal line with descriptors "no pain" at the initial point (score 0) and "worst pain" at the end point (score 100). To avoid clustering of scores, numbers or verbal descriptors at intermediate points are not recommended. Patients were asked to place a handwritten mark at one point along the 100mm line that best represents their pain intensity. The scores are recorded in millimeters and determined by the measurements from the initial point of the scale to the patients' mark, using a ruler. Higher scores indicate high levels of pain intensity. In this study, the scores (mm) of pain were recorded at days 7, 14, 21, 28, 60 and 90 and compared to the baseline score (day 0) to evaluate the response to each treatment.

    Time frame: 0,7,14,21,28,60,90 days

Secondary outcomes

  1. Change at Jaw Movements

    Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I was used to provide information of jaw movements. Using a caliper to assess mandibular range of motion (in millimeters), we measure mouth opening, right and left deviations and protrusion. This questionnaire was applied at baseline (day 0), end of the treatment (day 28) and follow up (day 90).

    Time frame: 0,28,90 days

  2. Change on Chronic Pain Grades

    RDC/TMD Axis II includes measures from the Graded Chronic Pain Scale (GCPS). Participants rated on scales from 0 = "no pain" to 10 = "pain as bad as could be" their current pain and average and worst facial pain in the past six months. Also, on scales from 0 = "no interference" to 10 = "unable to carry on any activities" the degree of facial pain interference with daily activities in the past six months. The mean of the ratings, multiplied by 10, gives information on characteristic pain intensity (CPI) and daily disability. The GCP is based on CPI, number of disability days in the past six months and daily disability score classified as 0 = no pain, I = low CPI and disability, II = high CPI and low pain-related disability, III = moderate CPI and disability, and IV = severe CPI and disability. In this study, the number of participants, at the end of the study, with Low Incapacity (Grades 0 to I) and Higher Incapacity (Grades II to IV) was compared to the baseline numbers.

    Time frame: 0,90 days

  3. Changes on Levels of Depression Symptoms

    RDC/TMD Axis II is a validated questionnaire which assess the levels of depression symptoms (LDS). The participants answered 20 questions about how much they have been distressed to several symptoms of depression rating on a scale: 0 =Not at all; 1= A little bit; 2=Moderately; 3=Quite a bit; 4=Extremely. The total number of participants in the end of study, with no depression (scores 0 and 1 on the scale) and with moderate and severe depression (scores 2 to 4 on the scale) was compared to the baseline numbers (day 0).

    Time frame: 0,90 days

  4. Change on Nonspecific Physical Symptoms With Pain

    RDC/TMD Axis II can be used to provide information on nonspecific physical symptoms with pain. The participants rate the experiences in the past few weeks relative to "how usually feels" about several pain symptoms as follows: 0 =Not at all; 1= A little bit; 2=Moderately; 3=Quite a bit; 4=Extremely. We divided the participants into no symptoms ("Normal" = scores 0 to1 at the scale) and moderate/severe symptoms (scale 2 to 4 at the scale) and compared the total number of participants in each classification (No symptoms and Moderate/severe symptoms) at the end of the study to the baseline numbers.

    Time frame: 0, 90 days

  5. Change on Nonspecific Physical Symptoms Without Pain

    RDC/TMD Axis II is also used to provide information on nonspecific physical symptoms without pain. The participants rate the experiences in the past few weeks relative to "how usually feels" about several symptoms nonrelated to pain as follows: 0 =Not at all; 1= A little bit; 2=Moderately; 3=Quite a bit; 4=Extremely. We divided the participants in no symptoms ("Normal" =scores 0 to1 at the scale) and moderate/severe symptoms (scale 2 to 4 at the scale) and compared the total number of participants in each classification at the end of the study to the baseline numbers.

    Time frame: 0, 90 days

  6. Changes on Mandibular Function

    The changes at mandibular functions can be evaluated using the question 19 of RDC/TMD Axis II. Participants answered 0=No (no limitation due to jaw problem) or 1=Yes (the activity is limited by the jaw problem - worse outcome) to a list of activities that the jaw problem can limit from doing. The mean of all the "Yes" answers (score 1) for each group in the end of the study (day 90) was calculated and compared to the baseline means.

    Time frame: 0, 90 days

  7. Changes on Levels of Anxiety

    Beck anxiety inventory (BAI) is a validated questionnaire with 21 multiple-choice items addressing how much the patient has been bothered by common symptoms of anxiety, at the list in the previous week. Each answer is scored on a scale value of 0 = not at all , 1=Mildly, but it didn't bother me much, 2=Moderately - it wasn't pleasant at times and 3=Severely - it bothered me a lot. We applied the BAI in two moments of the study (baseline and at follow -up= day 90). In each moment the participants were classified using a score calculated by finding the sum of the 21 items. Score of 0-21 = low anxiety, Score of 22-35 = moderate anxiety, Score of 36 and above = high levels of anxiety. We presented the results using only the mean of BAI of participants of each group in that moment. We compared the mean of BAI among the groups (PBM X MT X combined groups- intergroup analysis) in the baseline and follow-up period. In addition, we also analyzed intragroup results comparing the mean of BAI.

    Time frame: 0,90 days

06

Results

Posted Sep 26, 2019

Participant flow

Recruitment and follow-up assessment: May 2016 to November 2016. Location: Participants were recruited from patients referred to the Department of Buco Maxillofacial Surgery and Traumatology and to the Department of Conservative Dentistry at Federal University of Rio Grande do Sul, Porto Alegre,Brazil.

Participant flow — Overall Study
MilestonePhotobiomodulation GroupManual Therapy Group (MT)Combined Therapy Group (CT)
Started181617
Completed141314
Not completed433

Outcome measures

PrimaryChange From Baseline in Visual Analogic Scale (VAS) for Pain

Visual Analogic Score (VAS) is a psychometric scale used to measure subjective characteristics, as pain. Consists of a 100mm horizontal line with descriptors "no pain" at the initial point (score 0) and "worst pain" at the end point (score 100). To avoid clustering of scores, numbers or verbal descriptors at intermediate points are not recommended. Patients were asked to place a handwritten mark at one point along the 100mm line that best represents their pain intensity. The scores are recorded in millimeters and determined by the measurements from the initial point of the scale to the patients' mark, using a ruler. Higher scores indicate high levels of pain intensity. In this study, the scores (mm) of pain were recorded at days 7, 14, 21, 28, 60 and 90 and compared to the baseline score (day 0) to evaluate the response to each treatment.

Time frame:
0,7,14,21,28,60,90 days
Reported as:
Mean · millimeters
Change From Baseline in Visual Analogic Scale (VAS) for Pain
millimetersPhotobiomodulation GroupManual Therapy Group (MT)Combined Therapy Group (CT)
Baseline4.1 (2.91 to 5.36)4.4 (2.46 to 6.31)5.2 (3.75 to 6.61)
Day 73.3 (1.89 to 4.68)2.8 (1.51 to 4.03)3.4 (2.23 to 4.49)
Day141.9 (1.10 to 2.76)1.7 (0.71 to 2.68)2.4 (1.72 to 3.13)
Day 211.8 (0.77 to 2.8)0.5 (0.03 to 1.04)1.9 (1.12 to 2.59)
Day 281.1 (0.43 to 1.71)1.3 (0.17 to 2.44)0.9 (0.43 to 1.43)
Day 600.8 (0.19 to 1.39)0.6 (0.16 to 1.07)1.2 (0.72 to 1.71)
Day 901.6 (0.96 to 2.27)0.9 (0.17 to 1.66)1.9 (0.79 to 2.92)
Statistical analysis
  • Photobiomodulation Group vs Manual Therapy Group (MT) vs Combined Therapy Group (CT) · Regression, Linear · p = <0.001 · Mean difference (final values): 0.05
SecondaryChange at Jaw Movements

Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis I was used to provide information of jaw movements. Using a caliper to assess mandibular range of motion (in millimeters), we measure mouth opening, right and left deviations and protrusion. This questionnaire was applied at baseline (day 0), end of the treatment (day 28) and follow up (day 90).

Time frame:
0,28,90 days
Reported as:
Mean · millimeters
Change at Jaw Movements
millimetersPhotobiomodulation GroupManual Therapy Group (MT)Combined Therapy Group (CT)
Opening - Day 029.64 (27.17 to 32.35)27.92 (24.97 to 31.23)29.71 (25.49 to 34.64)
Opening - Day 2835.27 (29.53 to 35.92)34.00 (30.85 to 37.47)31.50 (29.27 to 33.90)
Opening - Day 9036.86 (34.51 to 39.36)33.38 (30.78 to 36.21)31.93 (30.41 to 33.52)
Maximum opening - day 040.86 (37.62 to 44.09)38.46 (35.06 to 41.86)35.29 (31.02 to 39.54)
Maximum opening - day 2842.79 (40.15 to 45.42)41.85 (39.60 to 44.09)38.93 (36.70 to 41.16)
Maximum opening - day 9044.50 (42.24 to 46.76)42.54 (39.56 to 45.51)39.93 (37.86 to 42.00)
Right excursion - day 05.93 (4.26 to 8.26)6.31 (5.13 to 7.76)6.57 (5.21 to 8.29)
Right excursion - day 288.36 (7.21 to 9.68)8.62 (6.91 to 10.74)6.64 (5.63 to 7.83)
Right excursion - day 907.90 (6.69 to 9.33)8.31 (7.06 to 9.78)7.36 (6.57 to 8.24)
Statistical analysis
  • Photobiomodulation Group vs Manual Therapy Group (MT) vs Combined Therapy Group (CT) · Generalized Estimating Equation · p = 0.05
SecondaryChange on Chronic Pain Grades

RDC/TMD Axis II includes measures from the Graded Chronic Pain Scale (GCPS). Participants rated on scales from 0 = "no pain" to 10 = "pain as bad as could be" their current pain and average and worst facial pain in the past six months. Also, on scales from 0 = "no interference" to 10 = "unable to carry on any activities" the degree of facial pain interference with daily activities in the past six months. The mean of the ratings, multiplied by 10, gives information on characteristic pain intensity (CPI) and daily disability. The GCP is based on CPI, number of disability days in the past six months and daily disability score classified as 0 = no pain, I = low CPI and disability, II = high CPI and low pain-related disability, III = moderate CPI and disability, and IV = severe CPI and disability. In this study, the number of participants, at the end of the study, with Low Incapacity (Grades 0 to I) and Higher Incapacity (Grades II to IV) was compared to the baseline numbers.

Time frame:
0,90 days
Reported as:
Count of participants · Participants
Change on Chronic Pain Grades
ParticipantsPhotobiomodulation GroupManual Therapy Group (MT)Combined Therapy Group (CT)
Day 0 — Low Incapacity10127
Day 0 — High Incapacity417
Day 90 — Low Incapacity13138
Day 90 — High Incapacity106
Statistical analysis
  • Photobiomodulation Group vs Manual Therapy Group (MT) vs Combined Therapy Group (CT) · Generalized Estimating Equation · p = 0.05
SecondaryChanges on Levels of Depression Symptoms

RDC/TMD Axis II is a validated questionnaire which assess the levels of depression symptoms (LDS). The participants answered 20 questions about how much they have been distressed to several symptoms of depression rating on a scale: 0 =Not at all; 1= A little bit; 2=Moderately; 3=Quite a bit; 4=Extremely. The total number of participants in the end of study, with no depression (scores 0 and 1 on the scale) and with moderate and severe depression (scores 2 to 4 on the scale) was compared to the baseline numbers (day 0).

Time frame:
0,90 days
Reported as:
Count of participants · Participants
Changes on Levels of Depression Symptoms
ParticipantsPhotobiomodulation GroupManual Therapy Group (MT)Combined Therapy Group (CT)
Day 0 — No depression673
Day 0 — Moderate/Severe depression8611
Day 90 — No depression1199
Day 90 — Moderate/Severe depression345
Statistical analysis
  • Photobiomodulation Group vs Manual Therapy Group (MT) vs Combined Therapy Group (CT) · Generalized Estimating Equation · p = <0.05
SecondaryChange on Nonspecific Physical Symptoms With Pain

RDC/TMD Axis II can be used to provide information on nonspecific physical symptoms with pain. The participants rate the experiences in the past few weeks relative to "how usually feels" about several pain symptoms as follows: 0 =Not at all; 1= A little bit; 2=Moderately; 3=Quite a bit; 4=Extremely. We divided the participants into no symptoms ("Normal" = scores 0 to1 at the scale) and moderate/severe symptoms (scale 2 to 4 at the scale) and compared the total number of participants in each classification (No symptoms and Moderate/severe symptoms) at the end of the study to the baseline numbers.

Time frame:
0, 90 days
Reported as:
Count of participants · Participants
Change on Nonspecific Physical Symptoms With Pain
ParticipantsPhotobiomodulation GroupManual Therapy Group (MT)Combined Therapy Group (CT)
Day 0 — Normal352
Day 0 — Moderate/Severe symptoms11812
Day 90 — Normal7106
Day 90 — Moderate/Severe symptoms738
Statistical analysis
  • Photobiomodulation Group vs Manual Therapy Group (MT) vs Combined Therapy Group (CT) · Generalized Estimating Equation · p = <0.01
SecondaryChange on Nonspecific Physical Symptoms Without Pain

RDC/TMD Axis II is also used to provide information on nonspecific physical symptoms without pain. The participants rate the experiences in the past few weeks relative to "how usually feels" about several symptoms nonrelated to pain as follows: 0 =Not at all; 1= A little bit; 2=Moderately; 3=Quite a bit; 4=Extremely. We divided the participants in no symptoms ("Normal" =scores 0 to1 at the scale) and moderate/severe symptoms (scale 2 to 4 at the scale) and compared the total number of participants in each classification at the end of the study to the baseline numbers.

Time frame:
0, 90 days
Reported as:
Count of participants · Participants
Change on Nonspecific Physical Symptoms Without Pain
ParticipantsPhotobiomodulation GroupManual Therapy Group (MT)Combined Therapy Group (CT)
Day 0 — Normal562
Day 0 — Moderate/Severe symptoms9712
Day 90 — Normal8118
Day 90 — Moderate/Severe symptoms626
Statistical analysis
  • Photobiomodulation Group vs Manual Therapy Group (MT) vs Combined Therapy Group (CT) · Generalized Estimating Equation · p = 0.05
SecondaryChanges on Mandibular Function

The changes at mandibular functions can be evaluated using the question 19 of RDC/TMD Axis II. Participants answered 0=No (no limitation due to jaw problem) or 1=Yes (the activity is limited by the jaw problem - worse outcome) to a list of activities that the jaw problem can limit from doing. The mean of all the "Yes" answers (score 1) for each group in the end of the study (day 90) was calculated and compared to the baseline means.

Time frame:
0, 90 days
Reported as:
Mean · score on a scale
Changes on Mandibular Function
score on a scalePhotobiomodulation GroupManual Therapy Group (MT)Combined Therapy Group (CT)
Chewing - day 00.5 (0.26 to 0.74)0.85 (0.55 to 0.96)0.93 (0.63 to 0.99)
Chewing - day 900.29 (0.11 to 0.56)0.38 (0.17 to 0.66)0.57 (0.32 to 0.79)
Exercising - day 00.07 (0.01 to 0.37)0.08 (0.01 to 0.39)0.50 (0.26 to 0.74)
Exercising - day 900.00 (0.00 to 0.00)0.08 (0.01 to 0.39)0.07 (0.01 to 0.37)
Eating hard foods - day 00.71 (0.44 to 0.89)0.85 (0.55 to 0.96)0.36 (0.16 to 0.62)
Eating hard foods - day 900.43 (0.21 to 0.68)0.54 (0.28 to 0.78)0.71 (0.44 to 0.89)
Eating soft foods - day 00.07 (0.01 to 0.37)0.23 (0.08 to 0.52)0.36 (0.16 to 0.62)
Eating soft foods - day 900.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.14 (0.04 to 0.43)
Smiling - day 00.36 (0.16 to 0.62)0.31 (0.12 to 0.59)0.50 (0.26 to 0.74)
Smiling - day 900.07 (0.01 to 0.37)0.08 (0.01 to 0.39)0.36 (0.16 to 0.62)
Swallowing - day 00.14 (0.04 to 0.43)0.23 (0.08 to 0.52)0.43 (0.21 to 0.68)
Swallowing - day 900.07 (0.01 to 0.37)0.00 (0.00 to 0.00)0.21 (0.07 to 0.49)
Statistical analysis
  • Photobiomodulation Group vs Manual Therapy Group (MT) vs Combined Therapy Group (CT) · Generalized Estimating Equation · p = 0.05
SecondaryChanges on Levels of Anxiety

Beck anxiety inventory (BAI) is a validated questionnaire with 21 multiple-choice items addressing how much the patient has been bothered by common symptoms of anxiety, at the list in the previous week. Each answer is scored on a scale value of 0 = not at all , 1=Mildly, but it didn't bother me much, 2=Moderately - it wasn't pleasant at times and 3=Severely - it bothered me a lot. We applied the BAI in two moments of the study (baseline and at follow -up= day 90). In each moment the participants were classified using a score calculated by finding the sum of the 21 items. Score of 0-21 = low anxiety, Score of 22-35 = moderate anxiety, Score of 36 and above = high levels of anxiety. We presented the results using only the mean of BAI of participants of each group in that moment. We compared the mean of BAI among the groups (PBM X MT X combined groups- intergroup analysis) in the baseline and follow-up period. In addition, we also analyzed intragroup results comparing the mean of BAI.

Time frame:
0,90 days
Reported as:
Mean · score on a scale
Changes on Levels of Anxiety
score on a scalePhotobiomodulation GroupManual Therapy Group (MT)Combined Therapy Group (CT)
Day 017.86 (8.56 to 27.15)14.92 (6.31 to 23.54)31.21 (21.93 to 40.49)
Day 909.57 (2.01 to 17.14)7.92 (3.93 to 11.91)13.57 (8.54 to 18.60)
Statistical analysis
  • Photobiomodulation Group vs Manual Therapy Group (MT) vs Combined Therapy Group (CT) · Generalized Estimating Equation · p = 0.05

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Photobiomodulation Group (PBM)—0/14 (0%)0/14 (0%)
Manual Therapy Group (MT)—0/13 (0%)0/13 (0%)
Combined Therapy Group (CT)—0/14 (0%)0/14 (0%)

Baseline characteristics

Age, Continuous
Age, Continuous(years)Photobiomodulation Group (PBM)Manual Therapy Group (MT)Combined Therapy Group (CT)Total
Mean46.29 ± 14.4342.44 ± 17.4541.65 ± 19.4643.48 ± 17.01
Sex: Female, Male
Sex: Female, Male(Participants)Photobiomodulation Group (PBM)Manual Therapy Group (MT)Combined Therapy Group (CT)Total
Female18151649
Male0112
Duration of pain
Duration of pain(years)Photobiomodulation Group (PBM)Manual Therapy Group (MT)Combined Therapy Group (CT)Total
Mean8.8 ± 6.910.1 ± 12.89.2 ± 99.4 ± 9.9
07

Study locations

No study locations are listed for this record.

08

Registry details

Key details

Study ID
NCT03454581
Lead sponsor
Federal University of Rio Grande do Sul
Responsible party
Manoela Domingues Martins (Associate Professor, Federal University of Rio Grande do Sul) — Principal investigator
First posted
Mar 6, 2018
Start date
May 17, 2016
Primary completion
Nov 14, 2016
Completion
Nov 14, 2016
Results posted
Sep 26, 2019
Last update
Sep 26, 2019

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Aug 2019. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion