Topical Menthol +/- Mannitol for Painful Diabetic Peripheral Neuropathy

NCT02728687 | Completed Phase 1

• 1 other identifier: M for PDPN
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 5

Brief Summary

Treatments for painful diabetic peripheral neuropathy (PDPN) are not very effective and have multiple side effects. To find out if a menthol cream alone or with added mannitol treats PDPN effectively, 90 participants with PDPN, after one month of observation, will receive randomly assigned menthol cream or the same cream with mannitol added for 3 months with a crossover for 3 additional months. At time 0, 1,4 and 7 months their BPI pain severity and interference scores, DN4 scores, cream % effectiveness and side effects will be compared.

Conditions

Diabetic Peripheral Neuropathy

Keywords

peripheral neuropathy; Diabetes; Pain

Outcome Measures

Primary Outcomes (1)

• BPI pain interference improvement 3 months

  Compares the change in BPI pain interference score after 3 months of cream use for menthol and mannitol cream and menthol cream alone.

  3 month

Secondary Outcomes (5)

• Maximum BPI pain severity improvement 3 months

  3 months

• NH4 improvement 3 month

  3 months

• % improvement from cream use

  3 months

• Satisfaction score

  3 months

• incidence of side effects

  3 months

Study Arms (2)

Mannitol and menthol cream

EXPERIMENTAL

Mannitol and menthol cream (Water, Mannitol, Propylene glycol, Isopropyl palmitate. Caprylic capric triglyceride, Ceteareth 20, Cetearyl alcohol, Glyceryl stearate, Polyethylene glycol 100 Stearate, Dimethicone, Octyldodecanol, Menthol, Lecithin, Ethylhexyl glycerin, Phenoxyethanol) applied as needed, up to 4 times daily for one month, to the feet of a person suffering from painful diabetic peripheral neuropathy. During the other month, the menthol cream will be applied to the participant's feet. Whether the mannitol and menthol cream will be given in the first or the second month will be chosen at random. At the end of the 2 months, if the participant chooses this cream, they will be given 3 months' supply of the cream to apply as needed to both feet.

Drug: Mannitol; Drug: Menthol

Menthol cream

ACTIVE COMPARATOR

Cream containing menthol (Water, Propylene glycol, Isopropyl palmitate. Caprylic capric triglyceride, Ceteareth 20, Cetearyl alcohol, Glyceryl stearate, Polyethylene glycol 100 Stearate, Dimethicone, Octyldodecanol, Menthol, Lecithin, Ethylhexyl glycerin, Phenoxyethanol) applied as needed, up to 4 times daily for one month, to the feet of a person suffering from painful diabetic peripheral neuropathy. During the other month, the mannitol and menthol cream will applied to the participant's feet. Whether the menthol cream will be given in the first or the second month will be chosen at random. At the end of the 2 months, if the participant chooses this cream, they will be given 3 months' supply of the cream to apply as needed to both feet.

Drug: Menthol

Interventions

Mannitol DRUG

Apply cream as needed up to 4 times daily to the painful foot and leg

Also known as: QR cream

Mannitol and menthol cream

Menthol DRUG

Apply cream as needed up to 4 times daily to the painful foot and leg

Mannitol and menthol cream; Menthol cream

Eligibility Criteria

• Age: 19 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 19 years of age or older
• Are currently being treated for diabetes with medications or insulin
• Suffering from painful diabetic peripheral neuropathy affecting their feet for at least three months.
• Maximum daily pain or discomfort score in each foot greater than or equal to 5/10.
• Score on the DN4 questionnaire at least 4/10
• At least 5 incorrect or I don't know responses to 8 on/off vibration tests
• Able and willing to attend Dr. Helene Bertrand's office three times.

You may not qualify if:

• Known Allergies to any of the ingredients of the cream
• Open lesions diabetic foot ulcers or abrasions on the skin where the cream will be applied
• Unwilling to stop using other topical products (creams or patches) for the treatment of their neuropathic pain at least 14 days before joining this study.
• Pain in each foot which varies by more than 2/10 from day-to-day
• Pregnant (a urine pregnancy test will be done on women younger than 50 at their first visit )
• breast-feeding,
• Women of reproductive age and not using the following methods of contraception:
• Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (DepoProvera, Lunelle), or hormone implant (Norplant System)
• Double-barrier method
• Non-hormonal intrauterine devices
• Vasectomy of partner
• Limited standing or walking from any cause (back, knees, feet, etc) other than diabetic neuropathic pain.
• Giving a history or exhibiting clinical signs of other causes of neuropathic pain such as spinal claudication, severe back pain on standing or walking, or a history of having received chemotherapy.
• Pain extending above the ankles.
• Those with ischemic peripheral vascular disease

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (5)

Private Physician's Office

Courtenay, British Columbia, V9N 2P6, Canada

Location

Okanagan Interventional Pain Clinic,

Kelowna, British Columbia, V1Y 4Z5, Canada

Location

Suite 303 - 570 Raymer Avenue, Kelowna, BC, Canada, V1Y 4Z5

Nelson, British Columbia, V1L 4C6, Canada

Location

Dr. Helene Bertrand Inc., 220-1940 Lonsdale Ave.

North Vancouver, British Columbia, V7M 2K2, Canada

Location

Maple Tree Medical Clinic

Salmon Arm, British Columbia, V1E 2S5, Canada

Location

Related Publications (6)

• Bertrand H, Kyriazis M, Reeves KD, Lyftogt J, Rabago D. Topical Mannitol Reduces Capsaicin-Induced Pain: Results of a Pilot-Level, Double-Blind, Randomized Controlled Trial. PM R. 2015 Nov;7(11):1111-1117. doi: 10.1016/j.pmrj.2015.05.002. Epub 2015 May 12.

  PMID: 25978942 BACKGROUND

• Daousi C, MacFarlane IA, Woodward A, Nurmikko TJ, Bundred PE, Benbow SJ. Chronic painful peripheral neuropathy in an urban community: a controlled comparison of people with and without diabetes. Diabet Med. 2004 Sep;21(9):976-82. doi: 10.1111/j.1464-5491.2004.01271.x.

  PMID: 15317601 BACKGROUND

• Young MJ, Boulton AJ, MacLeod AF, Williams DR, Sonksen PH. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia. 1993 Feb;36(2):150-4. doi: 10.1007/BF00400697.

  PMID: 8458529 BACKGROUND

• Duby JJ, Campbell RK, Setter SM, White JR, Rasmussen KA. Diabetic neuropathy: an intensive review. Am J Health Syst Pharm. 2004 Jan 15;61(2):160-73; quiz 175-6. doi: 10.1093/ajhp/61.2.160.

  PMID: 14750401 BACKGROUND

• Farrar JT, Young JP Jr, LaMoreaux L, Werth JL, Poole MR. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001 Nov;94(2):149-158. doi: 10.1016/S0304-3959(01)00349-9.

  PMID: 11690728 BACKGROUND

• Perkins BA, Olaleye D, Zinman B, Bril V. Simple screening tests for peripheral neuropathy in the diabetes clinic. Diabetes Care. 2001 Feb;24(2):250-6. doi: 10.2337/diacare.24.2.250.

  PMID: 11213874 BACKGROUND

MeSH Terms

Conditions

Peripheral Nervous System Diseases; Diabetes Mellitus; Pain

Interventions

Mannitol; Menthol

Condition Hierarchy (Ancestors)

Neuromuscular Diseases; Nervous System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Cyclohexanols; Hexanols; Fatty Alcohols; Cyclohexane Monoterpenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Monoterpenes; Terpenes; Lipids

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, CCFP, Clinical instructor, Department of family practice University of British Columbia

Study Record Dates

• First Submitted: March 30, 2016
• First Posted: April 5, 2016
• Study Start: March 15, 2017
• Primary Completion: March 30, 2020
• Study Completion: December 18, 2020
• Last Updated: March 2, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: As of April 15, 2019, 50 of the 90 participants have been entered into the study. At this rate, the study database should be completed by December 2020.
• Access Criteria: University affiliation. Peripheral neuropathy publication.

Locations

CA (5)