Diphenhydramine Ointment for Knee Osteoarthritis

Diphenhydramine 5% Ointment for Pain in Knee Osteoarthritis: a Randomised Double-blind Placebo-controlled Pilot Feasibility Study

The main purpose of this study is to evaluate whether recruitment rates are adequate to power a future RCT. The secondary aims are to obtain preliminary information about safety and efficacy of topical diphenhydramine 5% ointment in patients with knee OA.

Study Overview

• Status: Not yet recruiting
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: Diphenhydramine 5%; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ivan Shirinsky, MD, Doctor of Science; Phone Number: +73832282547; Email: ivan.shirinsky@gmail.com
• Study Contact Backup: Name: Valery Shirinsky, Professor, MD; Phone Number: +73832282547; Email: valery.shirinsky@gmail.com

Study Locations

• Russian Federation
  • Novosibirsk, Russian Federation, 630047
    • Laboratory of Clinical Immunopharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. ACR clinical criteria of knee OA
2. Radiographic knee OA (Kellgren-Lawrence grade >1)
3. Age ≥ 50 years
4. VAS pain >= 40/100 mm at baseline
5. Non-use of NSAIDs one week before the baseline
6. Symptoms present on most days for at least 3 months

Exclusion Criteria:

1. Any form of inflammatory arthritis
2. Use of another topical product at the application site
3. Treatment with intraarticular hyaluronic acid within 6 months
4. Treatment with intraarticular glucocorticoid within 2 months
5. Knee injury/surgery or diagnostic arthroscopy within 3 months
6. Allergic reaction to diphenhydramine or any component of the formulation
7. Participant has clinical signs and symptoms suggestive of COVID-19, eg, fever, dry cough, dyspnea, sore throat, fatigue or confirmed infection by appropriate laboratory test within the last 4 weeks prior to Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diphenhydramine; Topical 5% diphenhydramine ointment applied at knee joint at a dose of 2 g three times a day for 7 days	Drug: Diphenhydramine 5%; Diphenhydramine 5% ointment
Placebo Comparator: Placebo; Vehicle (placebo) ointment applied at knee joint at a dose of 2 g three times a day for 7 days	Drug: Placebo; Placebo matched to diphenhydramine 5% ointment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rates	Ability to recruit 8 patients per month	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Refusal rate	Number of eligible patients who refuse to participate	through study completion, an average of 1 year
Adherence	Number of patients adhering to 80% of allocated treatment	through study completion, an average of 1 year
Visual Analogue Scale for Pain	The Visual Analogue Scale for Pain varies from 0 to 10 cm. Higher values represent worse outcomes.	Baseline to week 1
Knee injury and Osteoarthritis Outcome Score (KOOS) - subscale Pain	KOOS Pain consists of 9 items, which are answered on a 4-point likert scale (0=no problems, 4=extreme problems). Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems..	Baseline to week 1
Knee injury and Osteoarthritis Outcome Score (KOOS) - subscale Symptoms	KOOS Symptoms consists of 7 items, which are answered on a 4-point likert scale (0=no problems, 4=extreme problems). Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems.	Baseline to week 1
Knee injury and Osteoarthritis Outcome Score (KOOS) - subscale Activities of daily living (ADL)	KOOS ADL consists of 17 items, which are answered on a 4-point likert scale (0=no problems, 4=extreme problems). Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems.	Baseline to week 1
Knee injury and Osteoarthritis Outcome Score (KOOS) - subscale of function in sports and recreation (Sport/Rec)	KOOS Sport/Rec consists of 5 items, which are answered on a 4-point likert scale (0=no problems, 4=extreme problems). Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems.	Baseline to week 1
Knee injury and Osteoarthritis Outcome Score (KOOS) - subscale of quality of life (QOL)	KOOS QOL subscale of quality of life consists of 4 items, which are answered on a 4-point likert scale (0=no problems, 4=extreme problems). Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems.	Baseline to week 1
Visual Analogue Scale for patient global assessment	The Visual Analogue Scale for patient global assessment varies from 0 to 10 cm. Higher values represent worse outcomes.	Baseline to week 1
Global evaluation of treatment by patient	Global evaluation of treatment by patient on 5 point Likert scale. The Global Evaluation of treatment varies from 0 to 5. Higher values represent worse outcomes.	Baseline to week 1
Percentage of patients achieving minimal clinically important improvement (MCII) of visual analogue scale (VAS) pain	Percentage of patients achieving MCII of VAS pain. The cut-off for MCII changes will be 15 of 100 for absolute improvement and 20% for relative improvement	Week 1
Percentage of patients achieving minimal clinically important improvement (MCII) of visual analogue scale (VAS) patient's global assessment	Percentage of patients achieving MCII of VAS patient's global assessment The cut-offs for MCII changes will be 15 of 100 for absolute improvement and 20% for relative improvement for patient's global assessment	Week 1
Percentage of patients achieving minimal clinically important improvement (MCII) of Knee injury and Osteoarthritis Outcome Score (KOOS) function of daily living	Percentage of patients achieving MCII of Knee injury and Osteoarthritis Outcome Score (KOOS) subscale of function of daily living. The cut-offs for MCII changes will be 8 of 100 for absolute improvement for KOOS function in daily living subscale score	Week 1
Adverse events	Any adverse event occurred during the study	Baseline to Week 1

Collaborators and Investigators

• Sponsor: Federal State Budgetary Scientific Institution, Research Institute of Fundamental and Clinical Immunology

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2021
• Primary Completion (Anticipated): April 1, 2022
• Study Completion (Anticipated): April 1, 2022

Study Registration Dates

• First Submitted: June 8, 2021
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): September 5, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: osteoarthritis; pain; knee; antihistamines
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Hypnotics and Sedatives; Anesthetics, Local; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Diphenhydramine; Promethazine
• Other Study ID Numbers: 415-5.13.04.2021-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No