controlled study of the efficacy ozone therapy in ... fa… · ozone in relation to local...

ControlledControlled StudyStudy of of thethe efficacyefficacy ozoneozonetherapytherapy in in FibromyalgiaFibromyalgia, , systemsystem reviewreview of of

a a randomisedrandomised controlledcontrolled trialtrial

Prof. Dr. med. Z. FahmyChief Consulting Rheumatologist

Augusta Clinic for Rheumatic DiseasesAnd Rhehabilitation Bad Kreuznach

Germany

MusculoskeletalMusculoskeletal PainPain SyndormSyndorm in in variousvarious RheumaticRheumatic diseasesdiseases

1.1. MyofascialeMyofasciale PainPain SyndromSyndrom((MyopathicMyopathic PainPain Syndrom)Syndrom)

2.2. FibomyalgiaFibomyalgia Syndrom (Syndrom (FibrositisFibrositis))

3.3. PolymyalgiaPolymyalgia rheumaticarheumatica

4.4. OsteoarthritisOsteoarthritis withwith high and high and lowlow tendertender pointspoints((cervicalcervical and and lumberlumber disordersdisorders))

MyopathicMyopathic painpain SyndromeSyndromeSymptoms and Finding:

n Localized in single muscle group or in groups of muscle

n The Trigger points in the muscle belly

n None or rare joint manifestations

n Pain Improved in rest and worse by exertion

n Sometimes not only the muscle involved, but also with muscle insertion (Tendinosis, Tendovaginosis etc.)

Fibromyalgia Syndrome

Symptoms and Finding:

-> tender points more than 18 points

-> Pain improved by moderate movement

-> Stronger physical strain will result in increasing pain

-> The patient mainly feel myalgia and arthralgia

ComparisonComparison of of FibrositisFibrositis//FibromialgiaFibromialgiaand and thethe myofacialmyofacial painpain syndromsyndrom

SpecificSpecificNonspecificNonspecificTreatment

Frequently observed; diagnostic Frequently observed; diagnostic when presentwhen present

??Local twitch response of muscle

Always some; depends on muscleAlways some; depends on muscle??Restricted range of motion

Whenever testableWhenever testable??Muscle weakness

OccasionallyOccasionallyBy definition, or usuallyBy definition, or usuallySkin-roll tenderness

Common especially with low serum folic and acid levels and thyroid function inadequacy

OftenOftenCold and weather sensitive

CommonBy definition, or 80% or moreBy definition, or 80% or moreSleep disorder

MuscleMuscle--specific pain patterns; if specific pain patterns; if untreated becomes chronicuntreated becomes chronic

Widespread and chronic (more Widespread and chronic (more than 3 months)than 3 months)

Pain

MyofascialMyofascial trigger points (any trigger points (any number)number)

Multiple (more than seven or more than 12) tender points

Tendernes

Equal numbers of males or femalesEqual numbers of males or femalesPredoninantly femaleSex

Common—50% male and female recruits

Uncommon—4% with primary and 11 concomitant fibrositis

Prevalence

MyofascialMyofascial Pain Pain SyndromSyndromFibrosis/Fibrosis/FibromialgiaFibromialgiaFeatureFeature

The aim of the study is to see the efficacy of ozone in relation to local anasthetic and Placebo

• Study design• Methods

1. 1. StudyStudy identificationidentification and and inclusioninclusion criteriacriteria2. 2. OutcomesOutcomes3. 3. Trial Trial qualityquality and and validityvalidity

4. 4. DataData extractionextraction and and synthesissynthesis

5. 5. ResultsResults

Trials and patients

a. efficacyb. discontinitations

Fibromyalgia clinical trialstudy groups: n = 300, age between 45 and 70

2-3x per weekover 4 weeks

2-3x per weekover 4 weeks

Lidocain 2%10 – 20 ml

15µg/ml10 – 100ml

placebolocalanaesthetic

ozone

Group 3 n = 100

Group 2n = 100

Group 1n = 100

n First group treated only with ozone

nn 22--3 3 timestimes weeklyweekly forfor oneone monthmonth

nn ConcConc.: 15 .: 15 µµg/ml; g/ml; volumevolume: 50: 50--100 ml; 100 ml; amountamount: 750 : 750 –– 1500 1500 µµg g ozoneozone

StudyStudy identificationidentification and and inclusioninclusion criteriacriteria

A. 3 A. 3 groupsgroups of of patientspatients withwith FibromyalgiaFibromyalgiaeacheach groupgroup n=100 n=100 patientspatients

nn Second Second groupgroup withwith locallocal anaestheticanaesthetic((lidocainlidocain) 4 ) 4 weeksweeks n = 1002 2 –– 3 3 timestimes weeklyweekly forfor oneone monthmonthLidocainLidocain 2% 2% ammountammount (10 (10 –– 20ml)20ml)

n Third group = Placebo group, n = 100

Age of Age of thethe patientspatients betweenbetween 45 and 7045 and 70

StudyStudy identificationidentification and and inclusioninclusion criteriacriteria

B. B. InclusionInclusion CriteriaCriteriaAbsolute Absolute indicationindication

Every patient must include these criteria

1. 1. PainPain intensityintensity at least 7 of at least 7 of thethe visualvisual analogueanaloguescalescale (VAS)(VAS)

2. 2. TheThe patientpatient mustmust havehave at least 13 at least 13 -- 18 18 pointspoints

3. 3. StiffnessStiffness at least 15 at least 15 minutesminutes

B. B. InclusionInclusion CriteriaCriteriaIf there is a NO, don't include the patientIf there is a NO, don't include the patient

1. Patient is aged 45 years old or over1. Patient is aged 45 years old or over2. The patient has been an outpatient for at least 4 weeks 2. The patient has been an outpatient for at least 4 weeks

3. FIBROMYALGIA according to the modified New3. FIBROMYALGIA according to the modified New--York criteriaYork criteria

Clinical criteriaClinical criteria

c. Low back pain of at least 3 months duration improvedc. Low back pain of at least 3 months duration improvedby exercise and not relieved by restby exercise and not relieved by rest

d. Limitation of motion of lumbar spine in d. Limitation of motion of lumbar spine in sagittalsagittal and frontal planesand frontal planes

e. Chest expansion decreased relative to normal values for age ae. Chest expansion decreased relative to normal values for age and sexnd sex

B. B. InclusionInclusion CriteriaCriteriaIIf there is a NO, don't include the patientf there is a NO, don't include the patient

5. Clinical axial involvement (back pain and/or buttock pain)5. Clinical axial involvement (back pain and/or buttock pain)

6. Without active (painful or swollen) peripheral arthritis 6. Without active (painful or swollen) peripheral arthritis lip and/or shoulder pain not included)lip and/or shoulder pain not included)

At the present time:At the present time:

7. Without clinical evidence of inflammatory bowel disease 7. Without clinical evidence of inflammatory bowel disease

8. The patient 8. The patient required a daily intake of any NSAIDrequired a daily intake of any NSAIDduring the last month at leastduring the last month at least

C. C. ExclusionExclusion CriteriaCriteriaIf there is a YES, don't include the patientIf there is a YES, don't include the patient

2. Concomitant treatment with 2. Concomitant treatment with sulfasalazinesulfasalazine, , methotrexatemethotrexateor any other disease modifying or any other disease modifying antirheumaticantirheumatic drugdruginitiated or with an altered dose preceding 6 monthsinitiated or with an altered dose preceding 6 months

1. 1. Consumption of more than 4 g Consumption of more than 4 g paracetamolparacetamol dailydaily

3. Concomitant treatment with an oral or 3. Concomitant treatment with an oral or parenteralparenteralcorticosteroid in the previous monthcorticosteroid in the previous month

4. IV corticosteroids with pulse therapy in the previous 2 4. IV corticosteroids with pulse therapy in the previous 2 monthsmonths

5. Intra5. Intra--articulararticular injections of corticosteroids in the previous injections of corticosteroids in the previous 3 months3 months

6. Concomitant treatment with anticoagulants including 6. Concomitant treatment with anticoagulants including heparin or with aspirinheparin or with aspirin

C. C. ExclusionExclusion CriteriaCriteria

7. Concomitant treatment with lithium or 7. Concomitant treatment with lithium or hydantoinshydantoins

8. The patient is pregnant, at risk of pregnancy 8. The patient is pregnant, at risk of pregnancy (inadequate contraception) or lactating (inadequate contraception) or lactating

9. Known hypersensitivity to analgesics, antipyretics and 9. Known hypersensitivity to analgesics, antipyretics and NSAIDsNSAIDs

10. Any clinical evidence of active peptic ulceration during 10. Any clinical evidence of active peptic ulceration during the previous 6 monthsthe previous 6 months

11. The patient has been included within the last month or11. The patient has been included within the last month oris currently participating in another clinical trialis currently participating in another clinical trial

12. Asthma induced by aspirin or other 12. Asthma induced by aspirin or other NSAIDsNSAIDs

C. C. ExclusionExclusion CriteriaCriteria

13.13. There is clinical evidence of, or known, severe:

f - mental illness

g - ulcerative colitis

h - inflammatory boweldisease

i - metabolic disease

a – cardiac disease

b - hepatic disease

c - renal disease

d - haematological disease

e – cancer

14.14. Any other Any other rheumatologicalrheumatological or nonor non--rheumatologicalrheumatologicaldisease which could interfere with the evaluation ofdisease which could interfere with the evaluation ofefficacy or safety of the treatmentefficacy or safety of the treatment

D. D. FunctionalFunctional Index of Index of FibromyalgiaFibromyalgiaRheumaticaRheumatica

For each question, a score of will be given

00 if the action can be accomplished without difficulty,if the action can be accomplished without difficulty,

0.5 0.5 if the action can be accomplished with sonic difficulties,if the action can be accomplished with sonic difficulties,

11 if the action can be accomplished with difficulties,if the action can be accomplished with difficulties,

1.5 1.5 if the action can be accomplished with great difficulties,if the action can be accomplished with great difficulties,

22 if it is impossible.if it is impossible.


Ask the patient the following questions Ask the patient the following questions and score the answerand score the answer

Are Are youyou ableable toto

1.put on your shoes

2.put on your trousers orpants

3.put on a pullover

4.get into the bath tub

5.stand still for 10 minutes

6. walk quickly

7. sit down

8. get up from a chair

9. get into a car

10. crouch down


Ask the patient the following questions Ask the patient the following questions and score the answerand score the answer

Are Are youyou ableable toto

11. bend over to pick something up

12. lie down

13. turn over in bed

14. get up from your bed

15. sleep on your back

16. sleep on yourstomach

17. deal with your workor housework

18. cough or sneeze

19. take a deep breath

n The efficiacy outcomes were common to trials in Fibromyalgia.

n Pain scale was measured using 10 cm visual analogue scale (VAS).

n Global rating of Fibromyalgia measuredusing function index:

2. 2. OutcomesOutcomes

unchangedunchanged> 20> 20moderatemoderate15 15 -- 2020

goodgood10 10 -- 1515veryvery goodgood1010

OVERALL PAIN DURING THE PREVIOUS OVERALL PAIN DURING THE PREVIOUS 48 HOURS48 HOURS

The patient will mark his/her score on a vertical line on the visual analogue scale.

„„HowHow intenseintense was was youryour painpain overover thethe last 48 last 48 hourshours??““

OVERALL PAIN DURING THE PREVIOUS 48 HOURS

No pain untolerable untolerable painpain

Distance between the patient mark and the Distance between the patient mark and the left end of the VAS : left end of the VAS :

A = I__I__I__IA = I__I__I__I mmmm

OVERALL PAIN DURING THE PREVIOUS OVERALL PAIN DURING THE PREVIOUS 48 HOURS48 HOURS

LABORATORY INVESTIGATIONSLABORATORY INVESTIGATIONS

The following samples are required at this visit:The following samples are required at this visit:

nn BIOCHEMISTRY SAMPLEBIOCHEMISTRY SAMPLE

nn HAEMATOLOGY SAMPLEHAEMATOLOGY SAMPLE

nn URINE SAMPLEURINE SAMPLE

TABLE OF CONTENTSTABLE OF CONTENTS

I FIRST PART OF V1 PLUS FIRST I FIRST PART OF V1 PLUS FIRST PART OF PART OF V2 (ELEGIBILITY CHECKS)V2 (ELEGIBILITY CHECKS)

•• Visit 1: Screening visitVisit 1: Screening visit

Availability of informed consent, Availability of informed consent, Demographic data, Demographic data, Inclusion criteria, Exclusion criteria, Inclusion criteria, Exclusion criteria, Overall pain assessment, Laboratory testsOverall pain assessment, Laboratory tests


I FIRST PART OF V1 PLUS FIRST PART OF V2 (ELEGIBILITY CHECKS)

n Visit 2 (Inclusion visit - D1)Eligibility checksInclusion criteria (continued) Allocation of treatment No

TABLE OF CONTENTSTABLE OF CONTENTSII SECOND PART OF V2PLUS V3 - V4 – V5

n Visit 2 (Continued)

Medical historyConcomitant diagnosesOverall assessment of disease activity Functional index Duration of morning stiffness Night painPhysical examination


nn Visit 3 Visit 3 -- 55

ComplianceComplianceNSAID consumptionNSAID consumptionConcomitant therapy/Adverse eventsConcomitant therapy/Adverse eventsOverall pain assessmentOverall pain assessmentOverall assessment of disease activity Overall assessment of disease activity Functional IndexFunctional IndexDuration of morning stiffnessDuration of morning stiffnessNight pain Night pain Physical examinationPhysical examination


nn Previous/Concomitant therapyPrevious/Concomitant therapy(from visit 2 to visit 5)(from visit 2 to visit 5)

Previous therapy with Previous therapy with NSAIDsNSAIDs tabletablePrevious and concomitant therapy Previous and concomitant therapy

table table Change in concomitant therapy tableChange in concomitant therapy tablenn Adverse events Adverse events ((from visit 2 to visit 5from visit 2 to visit 5))


nn Final assessments (V2 to V5)Final assessments (V2 to V5)

Global efficacy/Overall tolerabilityGlobal efficacy/Overall tolerabilityPhysical examination/Patient statusPhysical examination/Patient statusregarding AS (in case of withdrawal)regarding AS (in case of withdrawal)

nn Conclusion of patient participation Conclusion of patient participation (first 5 weeks of the trial)(first 5 weeks of the trial)

LABORATORY TESTSLABORATORY TESTS

(Option 1 = no (Option 1 = no centralizedcentralized laboratorylaboratory))

Date of samples : I__I__I I__I__I 200 I__Id d m m y

Trial Trial qualityquality and and validityvalidity

Clinical parameter for theefficiacy of the trial

• Visual analogue for the pain tendency

• Funktional score

• Medicine consumption

0

1

2

3

4

56

7

8

1.week 2.week 3. week 4. week 5.week

Group 1 with ozone Group 2 with local anasthetic Group 3 Placebo

Visual Visual analogueanalogue forfor thethe painpain tendencytendency

FunctionFunction indexindex scorescore

0

5

10

15

20

25

30

1. week 2. week 3. week 4. week 5. week

Group 1 with ozone Group 2 with local anasthetic Group 3 Placebo

MedicineMedicine consumptionconsumption

0

10

20

30

40

50

1. week 2. week 3. week 4. week 5. week

Group 1 (Patients 56 --> 48) Group 2 (Patients 68 --> 54)Group 3 (Patients 48 --> 40)

PreliminaryPreliminary ConclusionConclusion

1. Ozone has 1. Ozone has significantsignificant effecteffect in in FibromyalgiaFibromyalgia in in relationrelation to to thethe otherothertwotwo groupsgroups..

2. 2. FunctionFunction indexindex improvedimproved in in bothbothgroupsgroups ozoneozone and and anaestheticanaesthetic..

PreliminaryPreliminary ConclusionConclusion

3. Ozone treatment is a safe therapycompared to the local anasthetic.

4. Long terme therapy with ozone reducedpain in Fibromyalgia and

5. improved the life quality of the patients.

Vielen dank fVielen dank füür ihre r ihre AufmerksamkeitAufmerksamkeit

ThankThank youyou forfor youryour kindkind attentionattention

controlled study of the efficacy ozone therapy in ... fa… · ozone in relation to local...

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