Study NCT03860662
The Effect of Oral Baclofen and Botulinum Toxin Treatments in Hemiplegic Spasticity on the Nociceptive Flexor Reflex
Submitted Date:  June 18, 2021 (v3)
Quality Control Review Has Not Concluded

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Open or close this module Study Identification
Unique Protocol ID: MustafaKUPMR
Brief Title: The Effect of Oral Baclofen and Botulinum Toxin Treatments in Hemiplegic Spasticity on the Nociceptive Flexor Reflex
Official Title: Doctor, Physical Medicine and Rehabilitation
Secondary IDs:
Open or close this module Study Status
Record Verification: June 2021
Overall Status: Completed
Study Start: May 26, 2018
Primary Completion: March 21, 2019 [Actual]
Study Completion: April 21, 2019 [Actual]
First Submitted: February 8, 2019
First Submitted that
Met QC Criteria:		 March 1, 2019
First Posted: March 4, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
Last Update Posted: July 12, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Mustafa Kemal University
Responsible Party: Principal Investigator
Investigator: ERTURK GUNTURK
Official Title: research assistant doctor
Affiliation: Mustafa Kemal University
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: Yes
Unapproved/Uncleared Device:
Pediatric Postmarket Surveillance:
Data Monitoring: No
Open or close this module Study Description
Brief Summary: The purpose of this thesis is to research the effect of oral baclofen treatment and botulinum toxin injection treatments over the electromyographic nociceptive flexor reflex (NFR) threshold in hemiplegic patients with spasticity. The results of the study evaluated the Modified Ashworth Scale, joint range of motion, muscle strength, Brunnstrom stages, Barthel daily life activities index, electromyographic nociceptive flexor reflex (NFR) threshold.
Detailed Description:

Spasticity is defined as increased resistance tied to speed against passive movements and is related to hyperactive reflexes after upper motor neuron lesions. The hemiplegia table, which develops after subsiding, brings many problems along with it. Spasticity is one of these problems. Spasticity frequently leads to difficulty in the activities of daily life. It delays functional recovery, causes pain, and leads to secondary complications.

The objective of spasticity treatment minimizes the negative effects of hypertension without endangering function. Systematic medication treatment (baclofen, diazepam, dantrolen, and tizanidine) or local treatment (botulinum toxin, phenyl injection) are administered in spasticity treatment. The botulinum toxin prevents the secretion of acetylcholine in nerve endings and creates a presynaptic neuromuscular block. There are numerous studies that show that botulinum toxin is effective in spasticity.

Baclofen is a gamma aminobutyric acid (GABA) agonist. It passes through the blood-brain barrier and binds to the GABAb receptors of the spinal cord. Baclofen decreases spasms, clonus, and resistance to germs.

Various studies of electrophysiological reflexes are conducted to evaluate spasticity and to study neuronal circuits. The electrophysiological test is a tool used in studying the changes in spinal cord function and spinal reflexes in patients. The flexor reflex known as the recoil reflex is a polysynaptic and multisegmental reflex. It provides for avoidance and protection from internal and external stimulants that may be harmful for the body.

The purpose of the study is to research the effect of oral baclofen treatment and botulinum toxin injection treatments over the electromyographic nociceptive flexor reflex (NFR) threshold in hemiplegic patients with spasticity.

PURPOSE OF THE RESEARCH The purpose of this thesis is to research the effect of oral baclofen treatment and botulinum toxin injection treatments over the electromyographic nociceptive flexor reflex (NFR) threshold in hemiplegic patients with spasticity. The results of the study evaluated the Modified Ashworth Scale, joint range of motion, muscle strength, Brunnstrom stages, Barthel daily life activities index, electromyographic nociceptive flexor reflex (NFR) threshold
Open or close this module Conditions
Conditions: Stroke Sequelae
Spastic Hemiplegia
Keywords: Antispastic drugs
Nociceptive flexor reflex
Baclofen
Botulinum toxin
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 4
Interventional Study Model: Parallel Assignment
The purpose of this thesis is to research the effect of oral baclofen treatment and botulinum toxin injection treatments over the electromyographic nociceptive flexor reflex (NFR) threshold in hemiplegic patients with spasticity. The results of the study evaluated the Modified Ashworth Scale, joint range of motion, muscle strength, Brunnstrom stages, Barthel daily life activities index, electromyographic nociceptive flexor reflex (NFR) threshold.
Number of Arms: 2
Masking: Double (Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 29 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Active Comparator: Spastic hemiplegia , Botox
Botulinum toxin (BTX), being one of the most potent biological toxins, acts by blocking neuromuscular transmission via inhibiting acetylcholine release. Currently, focal spasticity is being treated successfully with BTX via injecting in the spastic muscles( Dose: 300-400 iu). Two antigenically distinct serotypes of BTX are available on the market as type A and B.
 Diagnostic Test: Nociceptor flexor reflex
The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response
Drug: Botox
botox
Spastic hemiplegia, Baclofen
Baclofen is an agonist that has presynaptic and postsynaptic effects on monosynaptic and polysynaptic pathways by binding to GABA B receptors. The recommended dosing regimen is initiated with 5 mg 3 times a day. It can be increased by 15-mg/d increments at 3-day intervals as needed. Dosing should not exceed 80 mg/d.
 Diagnostic Test: Nociceptor flexor reflex
The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response
Drug: Baclofen
baclofen
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. Thershold of Nociceptive Flexor Reflex
[ Time Frame: 6 weeks ]

The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Quality Control Review Comment provided by the National Library of Medicine:

  1. The description of the scale or categories does not include sufficient information to understand the results reported.
2. Barthel Index
[ Time Frame: 6 weeks ]

The Barthel Index (BI) measures the extent to which somebody can function independently and has mobility in their activities of daily living (ADL) i.e. feeding, bathing, grooming, dressing, bowel control, bladder control, toileting, chair transfer, ambulation and stair climbing. The index also indicates the need for assistance in care.The final score on the Barthel index ranges from 0, or complete dependence, to 100, or complete independence .
3. Vısual Analog Scale
[ Time Frame: 6 weeks ]

When using a VAS to assess pain, subjects are asked to indicate intensity by marking a (usually) 100-mm-long horizontal line that is labeled "no pain" at one end and "worst pain possible" at the other end. This requires the patient to be able to equate the length of the line (as measured from the left-hand side to the point marked) with the amount of pain they are experiencing. Higher values represent worse outcome.

Quality Control Review Comment provided by the National Library of Medicine:

  1. The description of the scale or categories does not include sufficient information to understand the results reported.
4. Modified Ashworth Scale
[ Time Frame: 6 weeks ]

The Modified Ashworth scale (MAS) measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Higher values represent worse outcome.

(0) No increase in muscle tone

(1) Slight increase in muscle tone, manifested by a catch and release or byminimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension.(1+) Slight increase in muscle tone, manifested by a catch, followed by minimalresistance throughout the remainder (less than half) of the ROM.(2) More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved.(3) Considerable increase in muscle tone, passive movement difficult.(4) Affected part(s) rigid in flexion or extension
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 60 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: Yes
Criteria:

Inclusion Criteria:

  • Being between the ages of 18-60
  • To accept voluntary participation in the study
  • Spastic Hemiplegia (Modified Ashworth Scale 2 and above)

Exclusion Criteria:

  • Pregnant women, breastfeeding and younger than 18 years
  • To have medication and substance use causing neuropathy in the history of the disease and / or neuropathy
  • Companies that have received botulinum toxin injection therapy and / or oral antispastic therapy within the last 6 months
  • Have a history of allergies and hypersensitivity to usability drug
  • Injection treatment planned purification hematoma, cleaning or skin lesion to be
Open or close this module Contacts/Locations
Locations: Turkey
Hatay Mustafa Kemal University
Hatay, Turkey
Open or close this module IPDSharing
Plan to Share IPD: Undecided
Open or close this module References
Citations:
Links:
Available IPD/Information:
Open or close this module Document Section
Study Protocol and Statistical Analysis Plan
Document Date: June 15, 2021
Uploaded: 06/18/2021 05:13
File Name: Prot_SAP_000.pdf

Quality Control Review Comment provided by the National Library of Medicine:

  1. Required information appears to be missing.
Study Results
Open or close this module Participant Flow
Recruitment Details
Pre-assignment Details
 
Arm/Group Title Spastic Hemiplegia , Botox Spastic Hemiplegia, Baclofen
Arm/Group Description

Botulinum toxin (BTX), being one of the most potent biological toxins, acts by blocking neuromuscular transmission via inhibiting acetylcholine release. Currently, focal spasticity is being treated successfully with BTX via injecting in the spastic muscles( Dose: 300-400 iu). Two antigenically distinct serotypes of BTX are available on the market as type A and B.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Botox: botox

Baclofen is an agonist that has presynaptic and postsynaptic effects on monosynaptic and polysynaptic pathways by binding to GABA B receptors. The recommended dosing regimen is initiated with 5 mg 3 times a day. It can be increased by 15-mg/d increments at 3-day intervals as needed. Dosing should not exceed 80 mg/d.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Baclofen: baclofen
Period Title: Overall Study
Started 15 14
Completed 15 14
Not Completed 0 0
Open or close this module Baseline Characteristics
Arm/Group TitleSpastic Hemiplegia , BotoxSpastic Hemiplegia, BaclofenTotal
Arm/Group Description

Botulinum toxin (BTX), being one of the most potent biological toxins, acts by blocking neuromuscular transmission via inhibiting acetylcholine release. Currently, focal spasticity is being treated successfully with BTX via injecting in the spastic muscles( Dose: 300-400 iu). Two antigenically distinct serotypes of BTX are available on the market as type A and B.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Botox: botox

Baclofen is an agonist that has presynaptic and postsynaptic effects on monosynaptic and polysynaptic pathways by binding to GABA B receptors. The recommended dosing regimen is initiated with 5 mg 3 times a day. It can be increased by 15-mg/d increments at 3-day intervals as needed. Dosing should not exceed 80 mg/d.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Baclofen: baclofen

Total of all reporting groups
Overall Number of Baseline Participants 15 14 29
Baseline Analysis Population Description [Not Specified]
Age, Categorical
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed15 Participants14 Participants29 Participants
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
15
100%
14
100%
29
100%
>=65 years
0
0%
0
0%
0
0%
Age, Continuous
Median (Full Range)
Unit of measure: years
Number Analyzed15 Participants14 Participants29 Participants
58(27 to 64)55(41 to 60)57(27 to 64)

Quality Control Review Comment provided by the National Library of Medicine:

  1. Information here appears inconsistent with information in other parts of the record.
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed15 Participants14 Participants29 Participants
Female
4
26.67%
5
35.71%
9
31.03%
Male
11
73.33%
9
64.29%
20
68.97%
Race and Ethnicity Not Collected [1]
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed15 Participants14 Participants29 Participants
0
 
[1]Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment
Measure Type: Number
Unit of measure: participants
Number Analyzed15 Participants14 Participants29 Participants
Turkey
151429
The patients' gender, age, weight, height, cerebrovascular case etiology, symptom durations and hemi
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed15 Participants14 Participants29 Participants
151429

Quality Control Review Comment provided by the National Library of Medicine:

  1. The measure does not appear to include sufficient information to understand how outcomes are measured and reported.
Modified Ashworth Scale - Ankle
Median (Full Range)
Unit of measure: units on a scale
Number Analyzed15 Participants14 Participants29 Participants
Modified Ashworth Scale - Ankle
3(3 to 4)3(2 to 4)3(2 to 4)
Brunnstrom - Hand
3(2 to 5)3(2 to 4)3(2 to 5)
VAS
3(2 to 5)3(2 to 4)3(2 to 5)
Barthel
50(20 to 85)50(30 to 65)50(20 to 85)
The nociceptive flexor reflex
8.1(4.2 to 12.0)8.1(4.2 to 10.2)8.1(4.2 to 12.0)

Quality Control Review Comment provided by the National Library of Medicine:

  1. The description of the scale or categories does not include sufficient information to understand the results reported.
Open or close this module Outcome Measures
1. Primary Outcome:
Title Thershold of Nociceptive Flexor Reflex
Description The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response
Time Frame 6 weeks

Quality Control Review Comment provided by the National Library of Medicine:

  1. The description of the scale or categories does not include sufficient information to understand the results reported.
Outcome Measure Data
Analysis Population Description
[Not Specified]
 
Arm/Group TitleSpastic Hemiplegia , BotoxSpastic Hemiplegia, Baclofen
Arm/Group Description

Botulinum toxin (BTX), being one of the most potent biological toxins, acts by blocking neuromuscular transmission via inhibiting acetylcholine release. Currently, focal spasticity is being treated successfully with BTX via injecting in the spastic muscles( Dose: 300-400 iu). Two antigenically distinct serotypes of BTX are available on the market as type A and B.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Botox: botox

Baclofen is an agonist that has presynaptic and postsynaptic effects on monosynaptic and polysynaptic pathways by binding to GABA B receptors. The recommended dosing regimen is initiated with 5 mg 3 times a day. It can be increased by 15-mg/d increments at 3-day intervals as needed. Dosing should not exceed 80 mg/d.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Baclofen: baclofen

Overall Number of Participants Analyzed15 14
Median (Full Range)
Unit of Measure: score on a scale
8.1(4.2 to 12.0) 10.0(4.2 to 12.0)
2. Primary Outcome:
Title Barthel Index
Description The Barthel Index (BI) measures the extent to which somebody can function independently and has mobility in their activities of daily living (ADL) i.e. feeding, bathing, grooming, dressing, bowel control, bladder control, toileting, chair transfer, ambulation and stair climbing. The index also indicates the need for assistance in care.The final score on the Barthel index ranges from 0, or complete dependence, to 100, or complete independence .
Time Frame 6 weeks
Outcome Measure Data
Analysis Population Description
[Not Specified]
 
Arm/Group TitleSpastic Hemiplegia , BotoxSpastic Hemiplegia, Baclofen
Arm/Group Description

Botulinum toxin (BTX), being one of the most potent biological toxins, acts by blocking neuromuscular transmission via inhibiting acetylcholine release. Currently, focal spasticity is being treated successfully with BTX via injecting in the spastic muscles( Dose: 300-400 iu). Two antigenically distinct serotypes of BTX are available on the market as type A and B.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Botox: botox

Baclofen is an agonist that has presynaptic and postsynaptic effects on monosynaptic and polysynaptic pathways by binding to GABA B receptors. The recommended dosing regimen is initiated with 5 mg 3 times a day. It can be increased by 15-mg/d increments at 3-day intervals as needed. Dosing should not exceed 80 mg/d.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Baclofen: baclofen

Overall Number of Participants Analyzed15 14
Median (Full Range)
Unit of Measure: score on a scale
55(25 to 85) 50(30 to 65)
3. Primary Outcome:
Title Vısual Analog Scale
Description When using a VAS to assess pain, subjects are asked to indicate intensity by marking a (usually) 100-mm-long horizontal line that is labeled "no pain" at one end and "worst pain possible" at the other end. This requires the patient to be able to equate the length of the line (as measured from the left-hand side to the point marked) with the amount of pain they are experiencing. Higher values represent worse outcome.
Time Frame 6 weeks

Quality Control Review Comment provided by the National Library of Medicine:

  1. The description of the scale or categories does not include sufficient information to understand the results reported.
Outcome Measure Data
Analysis Population Description
[Not Specified]
 
Arm/Group TitleSpastic Hemiplegia , BotoxSpastic Hemiplegia, Baclofen
Arm/Group Description

Botulinum toxin (BTX), being one of the most potent biological toxins, acts by blocking neuromuscular transmission via inhibiting acetylcholine release. Currently, focal spasticity is being treated successfully with BTX via injecting in the spastic muscles( Dose: 300-400 iu). Two antigenically distinct serotypes of BTX are available on the market as type A and B.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Botox: botox

Baclofen is an agonist that has presynaptic and postsynaptic effects on monosynaptic and polysynaptic pathways by binding to GABA B receptors. The recommended dosing regimen is initiated with 5 mg 3 times a day. It can be increased by 15-mg/d increments at 3-day intervals as needed. Dosing should not exceed 80 mg/d.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Baclofen: baclofen

Overall Number of Participants Analyzed15 14
Median (Full Range)
Unit of Measure: score on a scale
2(1 to 4) 2(1 to 3)
4. Primary Outcome:
Title Modified Ashworth Scale
Description

The Modified Ashworth scale (MAS) measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Higher values represent worse outcome.

(0) No increase in muscle tone

(1) Slight increase in muscle tone, manifested by a catch and release or byminimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension.(1+) Slight increase in muscle tone, manifested by a catch, followed by minimalresistance throughout the remainder (less than half) of the ROM.(2) More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved.(3) Considerable increase in muscle tone, passive movement difficult.(4) Affected part(s) rigid in flexion or extension

Time Frame 6 weeks
Outcome Measure Data
Analysis Population Description
[Not Specified]
 
Arm/Group TitleSpastic Hemiplegia , BotoxSpastic Hemiplegia, Baclofen
Arm/Group Description

Botulinum toxin (BTX), being one of the most potent biological toxins, acts by blocking neuromuscular transmission via inhibiting acetylcholine release. Currently, focal spasticity is being treated successfully with BTX via injecting in the spastic muscles( Dose: 300-400 iu). Two antigenically distinct serotypes of BTX are available on the market as type A and B.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Botox: botox

Baclofen is an agonist that has presynaptic and postsynaptic effects on monosynaptic and polysynaptic pathways by binding to GABA B receptors. The recommended dosing regimen is initiated with 5 mg 3 times a day. It can be increased by 15-mg/d increments at 3-day intervals as needed. Dosing should not exceed 80 mg/d.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Baclofen: baclofen

Overall Number of Participants Analyzed15 14
Median (Full Range)
Unit of Measure: score on a scale
2(1 to 3) 3(2 to 4)
Open or close this module Adverse Events
 
Time Frame No side effects were observed during the treatment and for 6 weeks after the treatment.
Adverse Event Reporting Description [Not specified]
 
Arm/Group Title Spastic Hemiplegia , Botox Spastic Hemiplegia, Baclofen
Arm/Group Description

Botulinum toxin (BTX), being one of the most potent biological toxins, acts by blocking neuromuscular transmission via inhibiting acetylcholine release. Currently, focal spasticity is being treated successfully with BTX via injecting in the spastic muscles( Dose: 300-400 iu). Two antigenically distinct serotypes of BTX are available on the market as type A and B.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Botox: botox

Baclofen is an agonist that has presynaptic and postsynaptic effects on monosynaptic and polysynaptic pathways by binding to GABA B receptors. The recommended dosing regimen is initiated with 5 mg 3 times a day. It can be increased by 15-mg/d increments at 3-day intervals as needed. Dosing should not exceed 80 mg/d.

Nociceptor flexor reflex: The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response

Baclofen: baclofen
All-Cause Mortality
  Spastic Hemiplegia , BotoxSpastic Hemiplegia, Baclofen
 Affected / At Risk (%)Affected / At Risk (%)
Total 0 / 15 (0%)0 / 14 (0%)
Serious Adverse Events
  Spastic Hemiplegia , BotoxSpastic Hemiplegia, Baclofen
 Affected / At Risk (%)Affected / At Risk (%)
Total 0 / 15 (0%)0 / 14 (0%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
  Spastic Hemiplegia , BotoxSpastic Hemiplegia, Baclofen
 Affected / At Risk (%)Affected / At Risk (%)
Total 0 / 15 (0%)0 / 14 (0%)
Open or close this module Limitations and Caveats
[Not specified]
Open or close this module More Information
Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact:
Name/Official Title:
 Dr. Erturk Gunturk
Organization:
 MustafaKU
Phone:
 +90 544 335 8637
Email:
 drerturkgunturk@gmail.com
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