What side effects are associated with this type of intervention?

Common treatments for ALS include riluzole and edaravone. Riluzole can cause side effects such as nausea, weakness, decreased lung function, and liver enzyme elevations. Edaravone is associated with side effects like bruising, gait disturbance, headache, and allergic reactions. Baricitinib, a JAK inhibitor being studied for ALS, has known side effects including headache, increased blood creatine phosphokinase, decreased neutrophil count, and nasopharyngitis. These side effects are consistent with those observed in other conditions treated with JAK inhibitors.

What prior FDA approvals exist?

The FDA has approved several treatments for Amyotrophic Lateral Sclerosis (ALS), including Riluzole and Edaravone. Riluzole works by inhibiting the release of glutamate, which may help protect nerve cells. Edaravone is thought to act as an antioxidant, reducing oxidative stress in the body. While Baricitinib, a Janus Kinase (JAK) inhibitor, is being studied for its potential in treating ALS due to its anti-inflammatory properties, there are no current FDA-approved JAK inhibitors specifically for ALS treatment.

What other types of research exist?

Promising novel alternatives to Baricitinib for ALS patients include: 1) Tofersen, an antisense oligonucleotide targeting SOD1 mutations, which has shown potential in clinical trials. 2) AMX0035, a combination of sodium phenylbutyrate and taurursodiol, which has demonstrated efficacy in slowing disease progression. 3) Reldesemtiv, a fast skeletal muscle troponin activator, which aims to improve muscle function and has shown positive results in clinical trials. These alternatives are currently being evaluated in clinical studies and may offer new hope for ALS patients.

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Janus Kinase (JAK) Inhibitor

Baricitinib for Alzheimer's & ALS (NADALS Trial)

Phase 1 & 2

Waitlist Available

Led By Mark W Albers, MD, PhD

Research Sponsored by Massachusetts General Hospital

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Must be 55-90 years old, inclusive and have subjective cognitive decline (SCD), minor neurocognitive disorder (mild cognitive impairment (MCI)), or major neurocognitive disorder (possible or probable AD)

Be older than 18 years old

Must not have

Previous therapy with baricitinib

Have had any major surgery within 8 weeks prior to screening or will require major surgery during the study

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, an average of 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests baricitinib, a pill taken daily, in people with early signs of Alzheimer's or ALS, or those at risk. The goal is to see if it can reduce harmful inflammation in the brain. Participants will take the medication for several months to check if it reaches the brain and lowers inflammation. Baricitinib is used for the treatment of rheumatoid arthritis and has shown promising preliminary data for moderate-to-severe atopic dermatitis.

Who is the study for?

Adults aged 55-90 with cognitive issues like Alzheimer's or mild impairment, and those aged 18-80 with ALS or carrying an ALS-related gene. Participants must have up-to-date vaccinations including Shingrix and COVID-19, be able to consent, and for those with AD, a MoCA score ≥8 plus a study partner is required. For ALS patients: stable on FDA treatments if any, able to walk at home daily, and life expectancy over 12 months.

What is being tested?

The trial tests baricitinib in participants with various neurodegenerative conditions over 24 weeks without using a placebo. It starts at a lower dose for the first eight weeks before doubling. The goal is to see if it can reach therapeutic levels in the brain/spinal fluid and reduce inflammation markers linked to these diseases.

What are the potential side effects?

Baricitinib may cause infections due to immune system suppression, changes in blood test results indicating liver or kidney issues, cholesterol increases, allergic reactions where the drug enters the body (if injected), digestive tract problems like diverticulitis or ulcers.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 55 and 90 years old and have been experiencing memory problems or have been diagnosed with a cognitive disorder.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with baricitinib before.

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I have not had major surgery in the last 8 weeks and do not need any during the study.

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I am not pregnant, breastfeeding, nor planning to become pregnant during the trial.

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I or a close family member have had blood clots in the lungs or deep veins.

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I have active ulcerative colitis, Crohn's disease, or had a peptic ulcer in the last 5 years or after 65.

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I have tested positive for tuberculosis.

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I have severe liver or kidney problems with low kidney function.

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I have had diverticulitis or a bowel perforation in the past.

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I am not on blood thinners that could make the trial unsafe for me.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, an average of 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, an average of 1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, an average of 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

CSF CCL2 Concentration

CSF Concentration of baricitinib

Secondary study objectives

CSF C-X-C motif chemokine ligand 10 (CXCL10) Concentration

CSF interferon gamma (IFNG) Concentration

CSF interleukin-6 (IL-6) Concentration

+8 more

Side effects data

From 2015 Phase 3 trial • 1307 Patients • NCT01710358

Nasopharyngitis

Pharyngitis

Urinary tract infection

Bronchitis

Back pain

Upper respiratory tract infection

100%

80%

60%

40%

20%

Study treatment Arm

Adalimumab Treatment B

BaricitinibTreatment B

Baricitinib Follow-up

Placebo Follow-up

Placebo Treatment B

Adalimumab Follow-up

Baricitinib Treatment A

Adalimumab Treatment A

Placebo Treatment A

Rescue

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: BaricitinibExperimental Treatment1 Intervention

Baricitinib 2mg administered by mouth once daily for the first 8 weeks, followed by baricitinib 4mg administered by mouth once daily for 16 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Baricitinib

2017

Completed Phase 3

~9510

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Amyotrophic Lateral Sclerosis (ALS) include medications like Riluzole and Edaravone, which work by reducing glutamate-induced excitotoxicity and oxidative stress, respectively. Baricitinib, a Janus Kinase (JAK) inhibitor, is being studied for its potential to suppress inflammatory pathways that contribute to motor neuron degeneration in ALS. By inhibiting JAK1 and JAK2, Baricitinib may reduce the inflammatory signaling that exacerbates neuronal damage. This is crucial for ALS patients as it targets the underlying inflammatory processes, potentially slowing disease progression and improving quality of life.