Ignite Creation Date:
2024-05-05 @ 6:34 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00501696
Status:
COMPLETED
Last Update Posted:
2008-05-19
First Post:
2007-07-12
Brief Title:
A Randomized Placebo-Controlled Crossover-Design Study of the Effects of Low Dose Naltrexone
Sponsor:
University of California San Francisco
Organization:
University of California San Francisco
Study Overview
Official Title:
A Randomized Placebo-Controlled Crossover-Design Study of the Effects of Low Dose Naltrexone on Quality of Life as Measured by the Multiple Sclerosis Quality of Life Inventory MSQLI54
Status:
COMPLETED
Status Verified Date:
2007-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a randomized placebo-controlled parallel-group study crossover-design of the effects of low dose naltrexone on the multiple sclerosis quality of life inventory MSQLI54
This study will assess the impact of LDN compared to placebo on quality of life as measured by the composite score of the MSQOL54 in adult subjects with MS
Also we plan
1 To compare the 10 scales of the MSQOL54 during the active treatment and placebo cycles between active treatment and placebo groups
2 To compare each individuals composite response to LDN versus placebo during the active treatment and placebo cycles
3 To compare each individual on the 10 scales of the MSQOL54 during the active treatment and placebo cycles
This study will assess the impact of LDN compared to placebo on quality of life as measured by the composite score of the MSQOL54 in adult subjects with MS
Also we plan
1 To compare the 10 scales of the MSQOL54 during the active treatment and placebo cycles between active treatment and placebo groups
2 To compare each individuals composite response to LDN versus placebo during the active treatment and placebo cycles
3 To compare each individual on the 10 scales of the MSQOL54 during the active treatment and placebo cycles
Detailed Description:
Immunomodulatory and immunosuppressive therapies are known to modify the course of the disease Interferon beta-1a interferon beta-1b and glatiramer acetate are immunomodulators whereas mitoxantrone and natalizumab are immunosuppressants
The disease modifying therapies decrease the frequency of relapses and are associated with improved neurological outcomes relative to placebo However these medications are only partially effective are expensive require either frequent self injections or intravenous infusion and have significant side effects None are proven in the progressive forms of MS and none of alleviate the symptoms associated with MS
Endogenous Opioid peptides and Naltrexone
Low dose naltrexone LDN is proposed to adjust the level of endorphins in the body thereby enhancing immune function and is anecdotally beneficial in MS LDN is inexpensive easily administered one capsule a day at bedtime and virtually has no serious side effect during the first weeks of LDN use some patients complain of some difficulty sleeping that rarely persists after the first week Although use of LDN is popular within the MS community efficacy is not proven because clinical trials have not been performed
Naltrexone is an opioid antagonist approved by the FDA in 1984 in a 50mg dose for the treatment of opioid and alcohol abuse By blocking opioid receptors naltrexone also blocks reception of the endogenous opioid peptides beta-endorphin metenkephalin and dynorphin Virtually every cell of the immune system has receptor for these mediators These peptides regulate a wide range of biological activities including immune responses through interaction with G-protein coupled transmembrane opioid receptors
In 1985 Bernard Bihari MD described the effects of low dose Naltrexone 15-45 mg Naltrexone on the bodys immune system He discovered that people with HIV had less than twenty percent of the normal level of endorphins He began looking for ways to raise endorphin without blocking its receptors and found that 175-45 mg Naltrexone Low Dose Naltrexone LDN at bed time raises the endorphin level up to 100 to 300 percent during the night Dr Bihari has reported beneficial effects of LDN on a variety of diseases such as cancers eg Multiple Myeloma Lymphoma Hodgkins disease breast cancer GI cancers non small cell cancer of lung malignant melanoma neuroblastoma ovarian cancer prostate cancer renal cell carcinoma and uterine cancer amyotrophic lateral sclerosis Alzheimers disease Behçets disease celiac disease chronic fatigue syndrome Crohns disease emphysema fibromyalgia HIVAIDS Irritable bowel syndrome Parkinsons disease pemphigoid psoriasis multiple sclerosis rheumatoid arthritis systemic Lupus erythematosus ulcerative colitis and Wegners granulomatosis Despite these anecdotal claims there are no published studies demonstrating efficacy of LDN in any disease state
Because of its low cost and ease of administration and anecdotal reports of efficacy LDN has gained a significant gross-roots following among patients and doctors There are some striking reports about beneficial effects of LDN on relapse reduction and disability and in general patients treated with LDN report improvements in a sense of well being fatigue as well as bowel bladder and sexual function
Immunological Mechanisms Involved in MS and effects of LDN β-endorphin is an opioid peptide synthesized by cells of the central nervous system arcuate nucleus and immune system lymphocytes thymocytes monocytes and splenocytes This peptide is decreased in concentration in peripheral blood mononuclear cells PBMC of MS patients with the lowest concentrations linked to the progressive forms of the disease Furthermore increased concentrations of β-endorphin are found during interferon beta treatment and following clinical relapses In the animal model of MS experimental autoimmune encephalitis β-endorphin blockade worsens disability
Lesions in MS may be the result of oligodendroglial apoptosis and microglial activation rather than neuroinflammatory processes Activated microglia secrete proinflammatory and neurotoxic factors nitric oxide and peroxynitrites that could cause neurodegeneration In theory inhibition of microglia would be protective in MS Naltrexone is capable of reducing microglial cytokine IL-1β and nitric oxide in glial cultures If naltrexone is beneficial in MS a possible mechanism of action is through reduction in microglial nitric oxide synthase activity resulting in decreased peroxynitrites production Peroxynitrites are thought to inhibit glutamate transporters thereby increasing the synaptic concentrations of glutamate resulting in excitatory neurotoxicity
The disease modifying therapies decrease the frequency of relapses and are associated with improved neurological outcomes relative to placebo However these medications are only partially effective are expensive require either frequent self injections or intravenous infusion and have significant side effects None are proven in the progressive forms of MS and none of alleviate the symptoms associated with MS
Endogenous Opioid peptides and Naltrexone
Low dose naltrexone LDN is proposed to adjust the level of endorphins in the body thereby enhancing immune function and is anecdotally beneficial in MS LDN is inexpensive easily administered one capsule a day at bedtime and virtually has no serious side effect during the first weeks of LDN use some patients complain of some difficulty sleeping that rarely persists after the first week Although use of LDN is popular within the MS community efficacy is not proven because clinical trials have not been performed
Naltrexone is an opioid antagonist approved by the FDA in 1984 in a 50mg dose for the treatment of opioid and alcohol abuse By blocking opioid receptors naltrexone also blocks reception of the endogenous opioid peptides beta-endorphin metenkephalin and dynorphin Virtually every cell of the immune system has receptor for these mediators These peptides regulate a wide range of biological activities including immune responses through interaction with G-protein coupled transmembrane opioid receptors
In 1985 Bernard Bihari MD described the effects of low dose Naltrexone 15-45 mg Naltrexone on the bodys immune system He discovered that people with HIV had less than twenty percent of the normal level of endorphins He began looking for ways to raise endorphin without blocking its receptors and found that 175-45 mg Naltrexone Low Dose Naltrexone LDN at bed time raises the endorphin level up to 100 to 300 percent during the night Dr Bihari has reported beneficial effects of LDN on a variety of diseases such as cancers eg Multiple Myeloma Lymphoma Hodgkins disease breast cancer GI cancers non small cell cancer of lung malignant melanoma neuroblastoma ovarian cancer prostate cancer renal cell carcinoma and uterine cancer amyotrophic lateral sclerosis Alzheimers disease Behçets disease celiac disease chronic fatigue syndrome Crohns disease emphysema fibromyalgia HIVAIDS Irritable bowel syndrome Parkinsons disease pemphigoid psoriasis multiple sclerosis rheumatoid arthritis systemic Lupus erythematosus ulcerative colitis and Wegners granulomatosis Despite these anecdotal claims there are no published studies demonstrating efficacy of LDN in any disease state
Because of its low cost and ease of administration and anecdotal reports of efficacy LDN has gained a significant gross-roots following among patients and doctors There are some striking reports about beneficial effects of LDN on relapse reduction and disability and in general patients treated with LDN report improvements in a sense of well being fatigue as well as bowel bladder and sexual function
Immunological Mechanisms Involved in MS and effects of LDN β-endorphin is an opioid peptide synthesized by cells of the central nervous system arcuate nucleus and immune system lymphocytes thymocytes monocytes and splenocytes This peptide is decreased in concentration in peripheral blood mononuclear cells PBMC of MS patients with the lowest concentrations linked to the progressive forms of the disease Furthermore increased concentrations of β-endorphin are found during interferon beta treatment and following clinical relapses In the animal model of MS experimental autoimmune encephalitis β-endorphin blockade worsens disability
Lesions in MS may be the result of oligodendroglial apoptosis and microglial activation rather than neuroinflammatory processes Activated microglia secrete proinflammatory and neurotoxic factors nitric oxide and peroxynitrites that could cause neurodegeneration In theory inhibition of microglia would be protective in MS Naltrexone is capable of reducing microglial cytokine IL-1β and nitric oxide in glial cultures If naltrexone is beneficial in MS a possible mechanism of action is through reduction in microglial nitric oxide synthase activity resulting in decreased peroxynitrites production Peroxynitrites are thought to inhibit glutamate transporters thereby increasing the synaptic concentrations of glutamate resulting in excitatory neurotoxicity
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None