Protocol summary

Study aim
To evaluate and compare the clinical efficacy in pain reduction and local safety of a topical omega 3 nanostructured lipid carrier gel versus a placebo gel in patients with mild to moderate knee osteoarthritis
Design
A phase 2, double blind, randomized, placebo controlled clinical trial with a parallel within person split body design on 30 patients using permuted block randomization and opaque sealed envelopes for allocation concealment
Settings and conduct
Eligible patients will be selected by an orthopedist at Shohada Hospital affiliated with Tabriz University of Medical Sciences. After obtaining informed consent, 30 patients will receive identical tubes with blinded codes؛ patients, the outcome assessor, and the data analyst will be blinded to the allocation.
Participants/Inclusion and exclusion criteria
Inclusion criteria include patients aged greater than or equal to 50 years with mild to moderate knee osteoarthritis and baseline pain score 2 to 7؛ Exclusion criteria include severe osteoarthritis, fish oil hypersensitivity, recent anti inflammatory or omega 3 use, recent knee injection or physical therapy, local skin disease, and body mass index greater than 30
Intervention groups
Intervention group: applies omega 3 nanostructured lipid carrier gel twice daily for four weeks on the assigned knee؛ Control group: applies placebo gel concurrently twice daily for four weeks on the contralateral knee
Main outcome variables
Change in knee pain intensity; change in knee inflammation severity

General information

Reason for update
Acronym
IRCT registration information
IRCT registration number: IRCT20130313012810N103
Registration date: 2026-06-11, 1405/03/21
Registration timing: registered_while_recruiting

Last update: 2026-06-11, 1405/03/21
Update count: 0
Registration date
2026-06-11, 1405/03/21
Registrant information
Name
Hamed Hamishehkar
Name of organization / entity
Drug Applied Research Center, Tabriz University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 41 1336 3311
Email address
hamishehkar.hamed@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2026-06-11, 1405/03/21
Expected recruitment end date
2026-07-12, 1405/04/21
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of the effects of a topical gel based on Nanostructured Lipid Carriers (NLC) loaded with Omega-3 compared to placebo on knee pain and inflammation in patients with knee osteoarthritis
Public title
Evaluation of a topical omega-3 gel for the reduction of pain and improvement of knee osteoarthritis
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Age greater than or equal to 50 years Confirmed diagnosis of knee osteoarthritis based on the American College of Rheumatology (ACR) clinical criteria Baseline pain score between 2 and 7 on the Visual Analog Scale (VAS) despite receiving standard care Radiographic evidence of knee osteoarthritis with Kellgren-Lawrence grade 1 to 3 Physical ability to apply the topical gel twice daily and attend all follow-up sessions Willingness to provide written informed consent and comply with study protocols
Exclusion criteria:
Presence of severe knee osteoarthritis with Kellgren-Lawrence grade 4 History of hypersensitivity or intolerance to fish oil, omega-3, or any component of the gel formulation Severe systemic comorbidities including uncontrolled diabetes (HbA1c greater than 9 percent), recent cardiovascular events, renal or hepatic impairment, or active malignancy Use of systemic anti-inflammatory drugs (NSAIDs, corticosteroids, biologics) or omega-3 supplements within the past 4 weeks Active skin diseases, open wounds, severe inflammation, redness, or extreme local warmth at the knee site preventing topical application Pregnancy, lactation, or planning to become pregnant during the study period Inability to ambulate without assistance or inability to complete assessments due to severe cognitive impairment History of intra-articular knee injections within the past 3 months Receipt of physical therapy or hydrotherapy for the knee within the past 3 months Presence of lower extremity radiculopathy, neuropathy, or other neurogenic conditions such as polio ​Concomitant pain in the hip or ankle joints that confounds the assessment of knee pain Body Mass Index (BMI) greater than 30 kilograms per square meter Secondary knee osteoarthritis resulting from previous bone fractures or trauma Requirement for concurrent treatment with regular systemic NSAIDs (except for a maximum of 10 tablets of 500 mg acetaminophen without codeine per month) Participation in any other clinical trial within the past 30 days
Age
From 50 years old
Gender
Both
Phase
2
Groups that have been masked
  • Participant
  • Outcome assessor
  • Data analyser
Sample size
Target sample size: 30
More than 1 sample in each individual
Number of samples in each individual: 2
Two evaluation units (left and right knees) will be assessed per participant; one knee serves as the intervention unit (receiving the Omega-3 nanostructured lipid carrier gel) and the contralateral knee serves as the control unit (receiving the placebo gel) for concurrent comparison.
Randomization (investigator's opinion)
Randomized
Randomization description
Randomization will be performed at the patient level to determine the treatment sequence for the knees (left vs. right) using a permuted block randomization method (with block sizes of 2 and 4). Each patient will be allocated to one of two sequences: Sequence A (Left knee: Omega-3 NLC gel; Right knee: Placebo gel) or Sequence B (Left knee: Placebo gel; Right knee: Omega-3 NLC gel). The unit of randomization is the individual patient. The allocation sequence will be generated using statistical software by an independent statistician who is not involved in clinical assessments. To ensure allocation concealment, sequentially numbered, opaque, sealed envelopes will be utilized. Upon enrollment of an eligible patient, the corresponding envelope will be opened in numerical order to determine which knee receives the active intervention and which receives the placebo.
Blinding (investigator's opinion)
Double blinded
Blinding description
The investigational products (Omega-3 NLC gel and placebo gel) will be identical in all physical characteristics, including color, odor, consistency, and packaging in identical tubes. The formulations will be prepared and labeled with unique codes (e.g., Gel A and Gel B) by the principal investigator (the formulation pharmacist), who is aware of the assignments but will have no role in the clinical enrollment, management, or evaluation of the patients. The participants (patients) will be fully blinded to which knee receives the active or placebo gel throughout the study. The outcome assessor (the clinician responsible for measuring and recording the VAS pain scores at baseline and at the end of the study) will also be completely blinded to the identity of the gels. Furthermore, the compiled data will be provided to the data analyst (statistician) in a coded format, and unblinding of the treatment codes will only occur after the statistical analysis has been fully completed.
Placebo
Used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Ethics committee of Tabriz University of Medical Sciences
Street address
Tabriz University of Medical Sciences, Daneshgah Street, Tabriz
City
Tabriz
Province
East Azarbaijan
Postal code
5165665811
Approval date
2026-05-24, 1405/03/03
Ethics committee reference number
IR.TBZMED.REC.1405.116

Health conditions studied

1

Description of health condition studied
Knee Osteoarthritis
ICD-10 code
M17
ICD-10 code description
Osteoarthritis of knee

Primary outcomes

1

Description
The severity of knee joint pain intensity in patients with mild to moderate osteoarthritis
Timepoint
At baseline before the intervention and four weeks after the start of the treatment
Method of measurement
Using the zero to ten centimeter visual analog scale questionnaire

2

Description
The severity of local inflammation and swelling in the knee joint area
Timepoint
At baseline before the intervention and four weeks after the start of the treatment
Method of measurement
Through local physical examination and knee joint palpation by an orthopedist specialist

Secondary outcomes

1

Description
The requirement and consumption amount of rescue analgesic medication by the patient during the study period
Timepoint
At baseline, two and four weeks after the start of the trial
Method of measurement
By counting the number of consumed acetaminophen tablets recorded in the patient daily diary log

Intervention groups

1

Description
Intervention group: 30 patients with bilateral knee osteoarthritis will topically apply an omega 3 nanostructured lipid carrier gel formulation twice daily (morning and evening) to the randomly assigned knee for a duration of one month (30 days). For each application, 1 gram of the gel will be applied topically to the affected knee areas. The formulation is prepared under standard laboratory conditions at the Drug Applied Research Center, Tabriz University of Medical Sciences, and packaged into identically coded tubes. The chemical composition of the gel consists of a lipid phase (omega 3 fatty acids, Precirol ATO 5, and gamma oryzanol), an aqueous surfactant phase (Tween 80 and Poloxamer), and a gel base matrix (Carbopol 940, triethanolamine, and distilled water). All participants will receive standardized education regarding proper topical application techniques and daily adherence protocols before initiating the trial.
Category
Treatment - Drugs

2

Description
Control group: The same patients will topically apply the placebo gel formulation twice daily (morning and evening) to the contralateral knee (opposite to the intervention knee) for a duration of one month (30 days). For each application, 1 gram of the gel will be applied topically to the affected knee areas. The formulation is prepared under standard laboratory conditions at the Drug Applied Research Center, Tabriz University of Medical Sciences, and packaged into coded tubes identical to the active gel. The chemical composition of the placebo gel is identical to the intervention gel except that Miglyol oil replaces the omega 3 fatty acids in the lipid phase (consisting of Miglyol, Precirol ATO 5, and gamma oryzanol)؛ while the aqueous surfactant phase (Tween 80 and Poloxamer) and the gel base matrix (Carbopol 940, triethanolamine, and distilled water) remain the exact same. All participants will receive standardized education regarding proper topical application techniques and daily adherence protocols before initiating the trial.
Category
Placebo

Recruitment centers

1

Recruitment center
Name of recruitment center
Shohada Hospital
Full name of responsible person
Hamed Hamishekar
Street address
Golshahr Street, El Goli Road
City
Tabriz
Province
East Azarbaijan
Postal code
5167846171
Phone
+98 41 3389 3336
Email
shohadahospital@tbzmed.ac.ir

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Khosro Adibkia
Street address
Drug Applied Research Center, Tabriz University of Medical Sciences, Daneshgah Street, Tabriz
City
Tabriz
Province
East Azarbaijan
Postal code
51656-65811
Phone
+98 41 3336 3311
Email
hamishehkar.hamed@gmail.com
Grant name
A student thesis with registration code 77481
Grant code / Reference number
77481
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tabriz University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic

Person responsible for general inquiries

Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Hamed Hamishehkar
Position
Professor
Latest degree
Ph.D.
Other areas of specialty/work
Medical Pharmacy
Street address
Drug Applied Research Center, Tabriz University of Medical Sciences, Daneshgah Street, Tabriz
City
Tabriz
Province
East Azarbaijan
Postal code
51656-65811
Phone
+98 41 3336 3181
Fax
+98 41 3336 3311
Email
hamishehkar.hamed@gmail.com
Web page address
http://darc.tbzmed.ac.ir/

Person responsible for scientific inquiries

Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Hamed Hamishehkar
Position
Associate professor
Latest degree
Ph.D.
Other areas of specialty/work
Medical Pharmacy
Street address
Drug Applied Research Center, Tabriz University of Medical Sciences, Daneshgah Street, Tabriz
City
Tabriz
Province
East Azarbaijan
Postal code
51656-65811
Phone
+98 41 3336 3181
Fax
+98 41 3336 3311
Email
hamishehkar.hamed@gmail.com
Web page address
http://darc.tbzmed.ac.ir/

Person responsible for updating data

Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Hamed Hamishehkar
Position
Professor
Latest degree
Ph.D.
Other areas of specialty/work
Medical Pharmacy
Street address
Drug Applied Research Center, Tabriz University of Medical Sciences, Daneshgah Street, Tabriz
City
Tabriz
Province
East Azarbaijan
Postal code
51656-65811
Phone
+98 41 3336 3181
Fax
+98 41 3336 3311
Email
hamishehkar.hamed@gmail.com
Web page address
http://darc.tbzmed.ac.ir/

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
No - There is not a plan to make this available
Statistical Analysis Plan
No - There is not a plan to make this available
Informed Consent Form
No - There is not a plan to make this available
Clinical Study Report
No - There is not a plan to make this available
Analytic Code
No - There is not a plan to make this available
Data Dictionary
No - There is not a plan to make this available
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