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Low-Dose Naltrexone for the Treatment of Painful Diabetic Neuropathy

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ClinicalTrials.gov Identifier: NCT04678895
Recruitment Status : Recruiting
First Posted : December 22, 2020
Last Update Posted : June 24, 2021
Sponsor:
Information provided by (Responsible Party):
Bruce M. Vrooman, Dartmouth-Hitchcock Medical Center

Brief Summary:
Diabetes affects more than 30 million people in the United States and is a leading cause of morbidity. Over 25% diabetics also suffer from debilitating painful diabetic neuropathy in the lower legs and feet. This pain can be severe, difficult to control, and have a significant negative impact on quality of life. Opioid medications have historically been a mainstay of treatment for this pain, despite the risks. As the death toll from the U.S. opioid epidemic continues to rise, the need for quality alternative non-opioid medications to treat pain becomes more urgent. One of these potential medications is Low-Dose Naltrexone (LDN). This drug is reported to work by enhancing the body's natural pain relieving mechanisms and decreases inflammation by targeting specific cells called microglia which have been shown to influence chronic pain. LDN has been shown to be a safe medication with minimal side effects. Its efficacy has been demonstrated in other painful conditions but has never been fully studied for treating painful diabetic neuropathy. The goal of this randomized, placebo-controlled trial is to determine if LDN is effective for treating the pain caused by diabetic neuropathy. LDN's mechanism of action is well suited to treating painful diabetic neuropathy, and LDN shows significant promise as a safe, non-opioid alternative that can decrease pain and improve quality of life for those suffering from this painful condition.

Condition or disease Intervention/treatment Phase
Painful Diabetic Neuropathy Drug: Naltrexone Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Randomized, double-blind, placebo-controlled, crossover trial.
Masking: Double (Participant, Investigator)
Masking Description: Investigational Pharmacy will perform the randomization process and remain unblinded throughout the study.
Primary Purpose: Treatment
Official Title: Low-Dose Naltrexone for the Treatment of Painful Diabetic Neuropathy, a Small, Randomized, Double-blind, Placebo-controlled Crossover Trial
Actual Study Start Date : December 22, 2020
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A, Low-Dose Naltrexone, Then Placebo
Group A will receive active drug (Naltrexone 1 capsule by mouth daily, 1.5mg x1 week, 3mg x1 week, and 4.5 mg x6 weeks) for the first 8 weeks. Capsules of different dosages will be indistinguishable. Then followed by 4 weeks of placebo (placebo capsule will be matched with LDN capsule, microcrystalline cellulose filler, 1 capsule daily).
Drug: Naltrexone
Capsule with doses of 1.5mg, 3mg, and 4.5 mg to allow for drug titration. Capsules of different dosages will be indistinguishable to allow for maintenance of blinding.

Drug: Placebo
Naltrexone matched placebo capsule.

Experimental: Group B, Placebo, Then Low-Dose Naltrexone
Group B will receive 4 weeks of placebo (placebo capsule will be matched with LDN capsule, microcrystalline cellulose filler, 1 capsule daily). Then followed by active drug (Naltrexone 1 capsule by mouth daily, 1.5mg x1 week, 3mg x1 week, and 4.5 mg x6 weeks) for the last 8 weeks. Capsules of different dosages will be indistinguishable.
Drug: Naltrexone
Capsule with doses of 1.5mg, 3mg, and 4.5 mg to allow for drug titration. Capsules of different dosages will be indistinguishable to allow for maintenance of blinding.

Drug: Placebo
Naltrexone matched placebo capsule.




Primary Outcome Measures :
  1. Change in Pain Disability Index [ Time Frame: Enrollment through week 12 ]
    Pain Disability index (PDI) Score measures the degree to which pain interferes with activities. Every item ranges from 0 (no interference) to 10 (total interference). The total PDI score can range from 0 to 70, a higher score indicating more interference with functioning across a range of activities.

  2. Change in Numeric Rating Scale for Pain [ Time Frame: Enrollment through week 12 ]
    Percent Change in Numerical Rating Scale (NRS) Scores Between Baseline to End of Placebo Treatment and Between Baseline to End of LDN Treatment. NRS is scored between 1-10 with 1 being no pain and 10 being the worst pain one can experience.


Secondary Outcome Measures :
  1. Ratio of Pain Catastrophizing Scores Compared to Change in Pain Disability Index [ Time Frame: Questionnaire will be administered on enrollment and compared to final pain score data, approximately 12 weeks. ]

    Assessment of the presence of pain catastrophizing behaviors based on the PCS and their effect in consideration of percent change with the Pain Disability Index. PCS is scored based on 13 questions with values ranging 0 to 4 for a total possible score of 52. The higher the score the more pain catastrophizing is present. Pain Disability index (PDI) Score measures the degree to which pain interferes with activities. Every item ranges from 0 (no interference) to 10 (total interference). The total PDI score can range from 0 to 70, a higher score indicating more interference with functioning across a range of activities.

    The result of these two measures will be expressed as a ratio of Change in PDI over PCS. If linear, we will use the ratio or an appropriate transformation as indicated by the data.


  2. Ratio of Pain Catastrophizing Scores Compared to Change in Numeric Rating Scale [ Time Frame: Questionnaire will be administered on enrollment and compared to final pain score data, approximately 12 weeks. ]

    Assessment of the presence of pain catastrophizing behaviors based on the PCS and their effect in consideration of percent change with the NRS. PCS is scored based on 13 questions with values ranging 0 to 4 for a total possible score of 52. The higher the score the more pain catastrophizing is present. NRS is scored between 1-10 with 1 being no pain and 10 being the worst pain one can experience.

    The result of these two measures will be expressed as a ratio of Change in NRS over PCS. If linear, we will use the ratio or an appropriate transformation as indicated by the data.


  3. Ratio of Pre-treatment Expectations Score Compared to Change in Pain Disability Index [ Time Frame: Questionnaire will be administered on enrollment and compared to final pain score data, approximately 12 weeks. ]

    Qualitative assessment of pre-treatment expectations, goals for treatment and confidence in the treatment based on a set of three questions.

    Each question will be assessed by a healthcare provider and scored between 1 to 5, 1 being low confidence towards treatment and 5 being very high confidence in treatment. Total possible score of 15. This will be compared to Change in Pain Disability Index. Pain Disability index (PDI) Score measures the degree to which pain interferes with activities. Every item ranges from 0 (no interference) to 10 (total interference). The total PDI score can range from 0 to 70, a higher score indicating more interference with functioning across a range of activities.

    The result of these two measures will be expressed as a ratio of Change in PDI over Pre-treatment Expectations Score. If linear, we will use the ratio or an appropriate transformation as indicated by the data.


  4. Ratio of Pre-treatment Expectations Compared to Change in Numeric Rating Scale [ Time Frame: Questionnaire will be administered on enrollment and compared to final pain score data, approximately 12 weeks. ]

    Qualitative assessment of pre-treatment expectations, goals for treatment and confidence in the treatment based on a set of three questions.

    Each question will be assessed by a healthcare provider and scored between 1 to 5, 1 being low confidence towards treatment and 5 being very high confidence in treatment. Total possible score of 15. This will be compared to Numeric Rating Scale. NRS is scored between 1-10 with 1 being no pain and 10 being the worst pain one can experience.

    The result of these two measures will be expressed as a ratio of Change in PDI over Pre-treatment Expectations Score. If linear, we will use the ratio or an appropriate transformation as indicated by the data.




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of Painful Diabetic Neuropathy (PDN) for >6 months
  2. Has failed at least one prior standard treatment for PDN (Gabapentin, duloxetine, etc)
  3. No other known causes of lower extremity neuropathic pain
  4. Subjects capable of giving informed consent
  5. Greater than 18 years of age
  6. Stable on all current non-opioid pain medication for at least 1 month
  7. English as primary language

Exclusion Criteria:

  1. Known allergy to naltrexone or naloxone
  2. Presence of known causes of lower extremity neuropathic pain not attributed to PDN
  3. Active substance use disorder or alcohol use disorder as defined by DSM-V
  4. Current treatment for substance use disorder or alcohol use disorder
  5. Current opioid therapy or on opioid therapy within the past 1 month

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04678895


Contacts
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Contact: Haley Johnson 603-653-0463 ext 30463 haley.j.johnson@hitchcock.org

Locations
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United States, New Hampshire
Dartmouth-Hitchcock Medical Center Recruiting
Lebanon, New Hampshire, United States, 03766
Contact: Annika M Brown, MD    603-650-4000    annika.m.brown@hitchcock.org   
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
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Study Director: Reuel J Measom, MD Dartmouth-Hitchcock Medical Center
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Responsible Party: Bruce M. Vrooman, Section Chief, Center for Pain and Spine, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT04678895    
Other Study ID Numbers: D20145
First Posted: December 22, 2020    Key Record Dates
Last Update Posted: June 24, 2021
Last Verified: June 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Bruce M. Vrooman, Dartmouth-Hitchcock Medical Center:
Low-Dose Naltrexone
Painful Diabetic Neuropathy
Additional relevant MeSH terms:
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Peripheral Nervous System Diseases
Diabetic Neuropathies
Pain
Neuromuscular Diseases
Nervous System Diseases
Neurologic Manifestations
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Naltrexone
Alcohol Deterrents
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents