ATLAS Therapy for Intermittent Claudication

(ATLAS Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Louis M Messina, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Massachusetts, Worcester

Must not be taking: PDE3 inhibitors, PDE5 inhibitors

Disqualifiers: Hypotension, Critical leg ischemia, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment to help people with pain and difficulty walking due to poor blood flow in their legs. The treatment includes three substances that aim to widen blood vessels and improve circulation. Researchers hope this will reduce pain and allow patients to walk longer distances.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications, specifically phosphodiesterase (PDE) 5 inhibitors like Viagra and Cialis, and PDE 3 inhibitors like cilostazol. The trial requires participants to discontinue these medications.

What data supports the effectiveness of the treatment ATLAS Therapy for Intermittent Claudication?

Research shows that supervised exercise therapy (SET) is effective for improving symptoms in patients with intermittent claudication, and adding supervision to exercise therapy can enhance its benefits. This suggests that ATLAS Therapy, which includes supervised exercise, may also be effective for this condition. ^{1 2 3 4 5}

Is ATLAS Therapy safe for humans?

Supervised exercise therapy (SET), a component of ATLAS Therapy, is generally safe for people with intermittent claudication, with very few adverse events reported. Home-based exercise programs (HBEPs) also show a low complication rate, suggesting that these exercise therapies are safe options for managing this condition. ^{2 6 7 8 9}

How is ATLAS Therapy different from other treatments for intermittent claudication?

ATLAS Therapy, or Supervised Exercise Therapy (SET), is unique because it involves structured, supervised exercise sessions that are more effective than unsupervised home-based exercise or simple walking advice. This approach ensures better adherence and outcomes by providing guidance and feedback, often using tools like accelerometers to track progress. ^{1 2 3 4 9}

Research Team

Louis M Messina, MD

Principal Investigator

UMASS Medical School

Eligibility Criteria

Adults over 18 with claudication from peripheral arterial disease (PAD) can join this trial if they have an Ankle-Brachial Index (ABI) <0.9, agree to stop certain medications like Viagra and Cilostazol, and use contraception if sexually active. Excluded are those with severe blood pressure issues, recent heart attacks or strokes, critical leg ischemia, kidney/liver problems, history of seizures or stones in the kidney.

Inclusion Criteria

I am older than 18 years.

I am willing to use birth control during the study.

Willing and able to provide informed consent

Exclusion Criteria

I have had a seizure before.

I need treatment with a drug that affects vitamin B9 use.

I have a severe illness like COPD or heart failure that makes it hard for me to walk.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ATLAS Therapy with two different doses of Tetrahydrobiopterin over 90 days

90 days

Regular visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ATLAS Therapy (Other)

Trial Overview The study tests whether a combination therapy including Tetrahydrobiopterin at two different doses along with L-Ascorbate and L-Arginine can boost Nitric Oxide production in the blood. This could potentially improve walking distance without pain for those with PAD.

Participant Groups

Group I: Tetrahydrobiopterin Dose 2 (Day 45 to 90) Experimental Treatment 3 Interventions

All subjects will receive 3300mg l-Ascorbate, l-Arginine 3400mg and 20mg/kg of Tetrahydrobiopterin once a day.

Group II: Tetrahydrobiopterin Dose 1 (Day 0 to 44) Experimental Treatment 3 Interventions

All subjects will receive 3300mg l-Ascorbate , l-Arginine 3400mg and 10mg/kg of Tetrahydrobiopterin once a day.

Who Is Running the Clinical Trial?

University of Massachusetts, Worcester

Lead Sponsor

Trials

372

Recruited

998,000+

Dr. Eric W. Dickson

University of Massachusetts, Worcester

Chief Executive Officer since 2013

MD from UMass Chan Medical School, Master's in Health Care Management from Harvard University

Dr. Andy Karson

University of Massachusetts, Worcester

Chief Medical Officer

MD

Louis Messina

Lead Sponsor

Trials

1

Recruited

10+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Dr. Richard J. Hodes

National Institute on Aging (NIA)

Chief Executive Officer since 1993

MD from Harvard Medical School

Dr. Marie Bernard

National Institute on Aging (NIA)

Chief Medical Officer

MD from Harvard Medical School

BioMarin Pharmaceutical

Industry Sponsor

Trials

162

Recruited

115,000+

Alexander Hardy

BioMarin Pharmaceutical

Chief Executive Officer since 2023

MBA from INSEAD

Greg Friberg

BioMarin Pharmaceutical

Chief Medical Officer

MD from New York Medical College

Findings from Research

The Network Exercise Therapy Parkstad has successfully trained 27 physiotherapists from 22 practices to provide supervised exercise therapy (ET) for patients with intermittent claudication, improving access to care in the Netherlands.

A web-based database has been established to facilitate communication between physiotherapists and vascular surgeons, ensuring continuous updates on patient information and enabling better monitoring of patient performance and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development and implementation of a regional network of physiotherapists for exercise therapy in patients with peripheral arterial disease, a preliminary report. Willigendael, EM., Bendermacher, BL., van der Berg, C., et al.[2018]

Exercise therapy significantly improves pain-free walking distance (PWD) and absolute walking distance (AWD) in patients with intermittent claudication, based on a systematic review of 15 studies involving 761 patients.

Supervised exercise therapy is more effective than standard care, showing an increase in PWD by 81.3 meters and AWD by 155.8 meters, but the added benefit of supervision over unsupervised exercise needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise therapy and the additional effect of supervision on exercise therapy in patients with intermittent claudication. Systematic review of randomised controlled trials. Wind, J., Koelemay, MJ.[2022]

Supervised exercise therapy (SET) significantly improves walking distance and quality of life in patients with intermittent claudication compared to just 'go home and walk' advice, with a median increase in walking distance of 310 meters for SET and 360 meters for SET with feedback after 12 months.

Providing daily feedback with an accelerometer alongside SET did not lead to additional improvements in walking distance or quality of life, suggesting that the structured exercise itself is the key factor in enhancing patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter randomized clinical trial of supervised exercise therapy with or without feedback versus walking advice for intermittent claudication. Nicolaï, SP., Teijink, JA., Prins, MH.[2015]

Supervised exercise therapy (SET) significantly improves maximal walking distance (MWD) and pain-free walking distance (PFWD) in patients with intermittent claudication compared to home-based exercise therapy (HBET) and walking advice (WA), with increases of approximately 120 and 210 meters after three months, respectively.

SET shows better outcomes for self-reported functional impairment and some quality of life measures compared to WA, while HBET does not demonstrate significant improvements over WA, indicating that SET is the most effective exercise intervention for enhancing walking capacity in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supervised exercise therapy versus home-based exercise therapy versus walking advice for intermittent claudication. Hageman, D., Fokkenrood, HJ., Gommans, LN., et al.[2022]

Supervised exercise therapy (SET) for patients with intermittent claudication (IC) is very safe, with only eight adverse events reported over 82,725 hours of training, resulting in a complication rate of just one event per 10,340 patient-hours.

The study suggests that routine cardiac screening before starting SET is unnecessary, which may encourage more healthcare providers to recommend this effective treatment for IC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of supervised exercise therapy in patients with intermittent claudication. Gommans, LN., Fokkenrood, HJ., van Dalen, HC., et al.[2022]

A survey of 84 vascular surgeons in the UK revealed that only 24% had access to supervised exercise programs for patients with intermittent claudication, despite strong recommendations for such programs from major clinical guidelines.

The study highlights a significant gap between evidence-based recommendations and actual practice, with 72% of respondents citing lack of resources as a barrier to implementing supervised exercise, which is known to improve patient outcomes and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supervised exercise for intermittent claudication - an under-utilised tool. Shalhoub, J., Hamish, M., Davies, AH.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

The development and implementation of a regional network of physiotherapists for exercise therapy in patients with peripheral arterial disease, a preliminary report. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Exercise therapy and the additional effect of supervision on exercise therapy in patients with intermittent claudication. Systematic review of randomised controlled trials. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Multicenter randomized clinical trial of supervised exercise therapy with or without feedback versus walking advice for intermittent claudication. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Supervised exercise therapy versus home-based exercise therapy versus walking advice for intermittent claudication. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Supervised walking therapy in patients with intermittent claudication. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of supervised exercise therapy in patients with intermittent claudication. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Real World Practice Deviation from Nationwide Guidelines in Patients with Intermittent Claudication. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Safety of home-based exercise for people with intermittent claudication: A systematic review. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Supervised exercise for intermittent claudication - an under-utilised tool. [2022]